OncologyLive® is the flagship publication of OncLive®. Each issue delivers expert insights and clinical oncology news and updates, which impact the day-to-day clinical practice of oncology professionals who work tirelessly to help improve patient outcomes.

The National Lung Screening Trial (NLST), a randomized, national trial involving 53,000 current and former heavy smokers, compared the effects of 2 screening procedures for lung cancer—low-dose helical computed tomography (CT) and standard chest x-ray&mdash; on lung cancer mortality. In November, the study authors reported 20% fewer lung cancer deaths among trial participants screened with CT scans.

In its wake, patient advocate groups are calling for swift implementation of national screening guidelines, while researchers are pursuing follow-on studies that will both refine testing protocols and expand the scope of the study.

The results were particularly striking because there are no early-screening protocols in place for lung cancer, and, in their absence, few of these tests are now performed. The disease kills nearly 80% of the approximately 200,000 people treated for it each year—more than any other cancer&mdash;in large part, researchers say, because the majority of lung cancers are detected at later stages. Participants in the trial were asymptomatic.

“Effective screening changes the nature of the disease,” noted Bruce E. Johnson, MD, director of the Lowe Center for Thoracic Oncology at the Dana-Farber Cancer Institute and a professor at Harvard Medical School, Boston, Massachusetts. “We take care of many lung cancer patients too often after the horse is out of the barn. Most people we see end up dying.”

“If we can change outcomes for 40,000 people a year, that would be almost the numbers of deaths from pancreatic and head and neck cancer combined,” said Mary E. Reid, PhD, an oncology professor and director of collaborative research for the Department of Medicine at Roswell Park Cancer Institute, Buffalo, New York.

NCCN Guideline Changes Are Under Consideration

Indeed, the results are so compelling that cancer experts, while noting that the study awaits peer review, are acting on them nonetheless.

“The control group in this study got chest x-rays, while the control in the real world gets nothing, so this may underestimate the true benefit,” said Douglas E. Wood, MD, a professor and chief  of general thoracic surgery at the University of Washington School of Medicine in Seattle. Wood, who is chairman of the lung cancer screening committee  for the National Comprehensive Cancer Network (NCCN), says the screening panel will likely release its guidelines by late spring.

“We have decided that we don’t need to wait for publication of the NLST results to publish our guidelines. A lot of people depend on the NCCN for guidance and our goal is to get the best data to physicians and patients as soon as possible,” he said. “It is no problem for us to refine our information as it becomes available. And we expect there will be new information coming that we will work in—better and more information.”

Wood declined comment on the guidelines, which will address both whom to screen and how best to screen, but noted that the NLST “gave us better data to talk about” and “a stronger validation of screening than any study that exists to date.”

He called publication and peer review important steps, while adding, “We’re enthusiastic and look to see details in forthcoming publications that validate the study results. And so, presuming that this follows as expected, this is an enormous, radical, major sea change in lung cancer detection and management—the largest in our lifetime.”

While cautioning that the NLST results apply only to the group studied, current or former heavy smokers who are 55 to 74 years old, Christine Berg, MD, chief of the NCI’s Early Detection Research Group and project officer for the study, said recently that individuals within that population “should have a conversation with their physicians about their options.”

Research studies that build on the NLST findings—some long underway and others still in the proposal stage&mdash;will refine its results by better defining the population of high-risk patients who would benefit most from screening and, following that, more invasive testing if nodules are discovered.

NCI points to studies indicating that 20% to 60% of screening CT scans of current and former smokers will show abnormalities, such as scars from smoking, areas of inflammation, and other noncancerous conditions. Most abnormalities are not lung cancer, the agency notes, and biopsies can cause partial lung collapse, among other complications. More major chest surgery to remove larger amounts of tissue poses even greater risks for patients with heart or lung conditions.

“The number of false positives is not trivial and so the clinical screening guidelines will have to be refined in the future,” said Reid.

The hunt for valid biomarkers to identify patients most likely to develop cancer is central to much of this research.

Avi Spira, MD, MSc, who leads a bioinformatics group at Boston University School of Medicine in Massachusetts, is among the researchers studying them. He is the principal investigator for a proposed early screening study, to be funded by the US Department of Defense, to identify molecular biomarkers that would indicate whether a patient with nodules of indeterminate malignancy is genetically susceptible to developing cancer. The researchers will examine cells collected from brushings from the lungs and scrapings from the nasal passages and mouth to see if they can detect genetic changes that would indicate whether those patients are likely to progress to cancer.

“There are several biomarkers that show promise, including gene expression studies from the cells in the airways, genetic changes in the lung tissues, whole-blood gene expression, proteomics, inflammatory markers, angiogenic markers, and epigenetic markers,” said Reid, who is the epidemiologist for the proposed study. “These are all currently under investigation to detect earlier lung cancers.”

Researchers say that the NLST itself will yield important new information upon further analysis that will also help refine screening protocols, including whether particular subgroups of participants, such as men, women, and some ethnic groups, benefited from the tests more than others. The study will continue to track participants.

“The findings from this study will become more mature,” Johnson said. “We’ll see what happens with the passage of time and whether the benefits expand or not. We’ll plug in real numbers about where distinctions are drawn, such as the age of participants and the number of packs smoked, for guidance on what to do for patients who do not fit within the design of the study.”

Additionally, more than 10,000 participants agreed to provide specimens of blood, urine, and sputum at each of their annual screens to establish a biorepository that will support research on molecular biomarkers of early lung cancer. All NLST participants who underwent lung cancer resection were invited to provide small samples of the resected tumors to supplement the biorepository.

Existing imaging technology is also a powerful tool for monitoring nodules that can be “delivered in an economic fashion,” said James L. Mulshine, MD, vice president for research and associate provost for research at Rush University Medical Center, Chicago, Illinois.

While stressing the need for “rigorous clinical trials,” Mulshine pointed to research studies “that suggest we can leverage the rapid improvements in CT imaging to further assist with the management process of lung cancer screening. We can segregate nodules that are clinically aggressive from those with no growth.”

Based upon their review of the NST findings and continuing improvements in imaging capability, patient advocacy groups are calling on government regulators to “swiftly translate this scientific validation into a public health benefit in a safe, uniform and cost effective way,” as Laurie Fenton Ambrose, president and chief executive officer of

“Screening for lung cancer is not automatically covered like mammography, PSAs [prostate-specific antigen tests], and colonoscopies,” Ambrose said. “But now with the National Cancer Institute’s validation of the lung cancer screening mortality benefit, government screening recommendations for lung cancer should be revised to reflect this new development. This would then trigger changes in public and private coverage.”

Shortly after the NLST findings were released, Ambrose, with the heads of other patient advocacy groups, wrote to the director of the Agency for Healthcare Research and Quality (AHRQ) to urge the agency to review its screening recommendations for lung cancer.

The AHRQ, which is part of the US Department of Health and Human Services, provides administrative, technical, and research support to the US Preventive Services Task Force (USPSTF), an independent panel of experts that conducts scientific evidence reviews of clinical preventive healthcare services and develops recommendations for primary care clinicians and health systems. The USPSTF’s current recommendation is an “I,” meaning the task force believes there is insufficient evidence to recommend for or against screening asymptomatic persons for lung cancer with either low-dose CT, chest x-ray, sputum cytology, or a combination of these tests.

“While it is our understanding that USPSTF’s standard practice is to review all topics on a 5-year schedule, we urge that a review commence immediately, given the irrefutable evidence provided by the analysis of the NLST data,” Ambrose and the others wrote.

The task force, however, does not plan to consider updating its recommendation until 2012, Ambrose said she has since learned.

“I am disappointed that a now proven benefit that could save tens of thousands of lives has not been more positively and aggressively embraced. I do not see a sense of urgency among public health leaders and medical professionals to translate this benefit into public health infrastructure,” she commented.

Advocates for lung cancer patients contend that the demonization of tobacco use—and patients by association&mdash;has caused research into one of the most complex cancers to lag well behind that of diseases with greater political support.

“Lung cancer is the most stigmatized and ignored of all cancers and for decades has lacked a comprehensive public health strategy. That is because lung cancer is viewed singularly as tobacco driven, when it is in fact more complex than that,” Ambrose said, adding that the majority of people diagnosed with the disease are former smokers who heeded public health messages to quit.

Researchers do not disagree with her assessment, noting that basic science around the disease has been comparatively slow to emerge.

“It’s as if it’s not random, as if they did it to themselves,” Reid said of the perceptions of lung cancer patients. “Only 1 to 2 out of 10 smokers and former smokers will get lung cancer. My chance of breast cancer is 1 out of 7. I have risk factors, some behavioral, that increase my risk of breast cancer.” She added, “With breast cancer screening, there are questions about whether it changes mortality, and about whether we should do it once every 1 or 2 years. But there is an overwhelming advocacy there. Who is going to look a woman in the eye and say no to screening? The insurance companies aren’t either. With the PSA test, too, results are unclear. It’s not that there is no controversy, but there is a huge advocacy.”

Wood noted that in the absence of protocols, amid the “high bar that has been set for evidence-based medicine,” few early tests are now performed. “To date, physicians are not really promoting lung cancer screening. It’s predominantly patients who are assertive, proactive, or nervous, who seek it for themselves,” he said, adding that it is often detected “during a chest x-ray or CT scan for something else.”

Earlier screening studies, involving chest x-rays and sputum analyses, proved inconclusive. The International Early Lung Cancer Action Program (I-ELCAP), which used CT screening to detect early lung cancer, reported results in 2006 that suggested that CT screening might be beneficial. It was a nonrandomized trial, however, that did not use mortality as the endpoint.

Researchers say that effective screening modalities became available in the 1990s with the advances provided by CT scans.

“The technology from CT scans was much better in terms of accuracy and efficiency. We had information by 1999 that one could pick up nodules as small as 2 mm that when resected were usually the earliest stage lung cancer—stage IA,” Johnson recalled. “The findings from the study were used for the NLST design, and the trial started in 2002.” (Henschke CI, et al. 

Berg noted that while the test was available, “it was conducting a trial of this size and cost to determine true validity that took time. Lung cancer is actually many diseases, some of which are highly aggressive, much more so than breast cancer, so technology had to advance and be studied appropriately to actually find an intervention that was effective in detecting the cancers early enough in their natural history to have an impact.”

Low-dose helical CT, also known as spiral CT, uses x-rays to scan the entire chest in about 7 to 15 seconds during a single breath-hold. The CT scanner rotates around the person, who is lying still on a table as the table passes through the center of the scanner. A computer creates images from the x-ray information coming from the scanner and then assembles these images into a series of 2-dimensional slices of the lung at very small intervals so that increased details within the organs in the chest can be identified.

Researchers say its accuracy of detection over many prospective trials has proved to be >90%. And while there is some concern about the exposure from repeated CT scans, those risks are weighed against the short life expectancy of patients who develop lung cancer.

“I don’t see any other screening modality employed in a broad population of subjects at risk in the next decade,” Johnson said.

Mulshine also noted that it is quick, not painful, and “deployed everywhere—and the cost of the technology for an individual study is not expensive.” Each scan costs from $300 to $1000, according to the NCI.

But while the technology is widely available, screening procedures will have to be implemented carefully, Mulshine added. “Going forward, there are cost issues, quality issues, and issues around support services. How effective and safe will this be? What are the triggers for more testing and what are the quality controls?”

Ambrose is working with members of Congress to establish a demonstration program.

“We need to make sure there is proper guidance around screening protocols, as screening is not a procedure, it is a process. In other words, it is more than a picture. It is a process for managing what is found,” she said. “This is why we are calling for a federal lung cancer demonstration screening program as part as of the Lung Cancer Mortality Reduction Act, just as was done for mammography and colonoscopy to ensure that the screening protocol is tested before best practices are standardized and uniformly adapted within the broader public health infrastructure.”

Johnson said it is also important to make sure that screening is deployed effectively and efficiently.

“The group at risk of lung cancer tends not to be the group that takes the best care of itself. People who smoke a lot may not have an internist, for example. We need to make sure these patients have access to the screening and there is appropriate follow-up for them,” he said.

“Cancer deaths are falling wherever we have effective screening, which is true in breast, prostate, and colon cancer. The discussion around cost is a solvable problem, and having an effective screening is a first step,” he added. “It’s the responsibility of the medical community to see that screening can be done in a way that’s reasonable for both subjects at risk and for the third-party payers.”

Articles

The National Lung Screening Trial (NLST), a randomized, national trial involving 53,000 current and former heavy smokers, compared the effects of 2 screening procedures for lung cancer

A Leap in Lung Cancer Care: Early-Screening Success Prompts Push for Change

Organization Specializes in Head and Neck Cancers

	The American Head and Neck Society (AHNS) is the largest organization in America dedicated to advancing head and neck cancer research and education. The AHNS official Website features a number of resources for clinicians, including a link to the society’s official publication, 

Archives of Otolarynogology — Head & Neck Surgery

, which also has a collection of videos and CME courses. In the clinical resources section of the site, visitors can find practice guidelines for many head and neck cancer  topics, including general guidelines for surgery, chemotherapy, imaging, and radiotherapy, as well as guidelines for tumors of the upper aerodigestive tract, tumors of major salivary glands, tumors of the thyroid, and other head and neck tumors. The site also has a job board, where clinicians involved in the treatment of head and neck cancers are able to seek or offer positions for head and neck oncology programs. Information on the society’s annual meeting may be found in the meetings and events section, which also contains downloadable programs for previous AHNS and other head and neck cancer conferences and meetings.

MedicineNet.com — “Head and Neck Cancer”

	MedicineNet.com is a Website designed to provide detailed and accurate information to nonprofessionals on a wide range of medical topics, including head and neck cancer. The section on head and neck cancer discusses a number of issues that patients or their loved ones might have questions about, including what cancer is, what kinds are considered head and neck cancers, what causes them, what their common symptoms are, how they are diagnosed and treated, whether follow-up treatment is necessary, and more. There are also links to articles recommended by MedicineNet. com’s medical professionals that cover related diseases and conditions, medications, procedures and tests, expert views, and other subjects. Key terms throughout the information found on the site are highlighted and serve as direct links to their definitions in MedicineNet. com’s glossary.

www.medicinenet.com/head_and_neck_cancer/article.htm

	This CME activity is based on highlights from the 2010 NCCN Respiratory Tract Cancers Congress and focuses on the management of head and neck cancers, lung cancers, and metastases to the central nervous system. The activity includes a Webcast of multiple experts presenting the various points covered in the activity. These presentations are accompanied by a slideshow (which may also be downloaded separately) containing relevant charts, diagrams, and information. The topics in this CME concerning head and neck cancer include the role of induction chemotherapy in its primary treatment, its surgical management, its biomarkers, how it is connected to the human papillomavirus, and how advanced head and neck cancers are managed. The other parts of the CME focus on choosing the best therapies for patients with localized and advanced non-small cell lung cancer, limited-stage and extensive-stage small cell lung cancer, and patients with metastases to the central nervous system. 

Brachytherapy With Permanent Gold Grain Seeds for Squamous Cell Carcinoma of the Lip

This study evaluated the use of radioactive gold grain implantation for the treatment of squamous cell carcinoma of the lip. For this study, 51 patients who had been treated with permanent gold grain implant brachytherapy were retrospectively reviewed. The seeds delivered a dose of 5500cGy at 0.5 cm from a single plane. The primary endpoints of the study were local recurrence and cosmetic outcome.

 The median follow-up and age was 27 months and 69 years, respectively. In all, 90% of the cases reviewed were T1 lesions; 12 of the patients had recurrent disease with prior surgery and 5 patients had previous head and neck radiation. None had evidence of regional lymph node or distant metastasis. Of the 51 patients reviewed, local control was achieved in 49 and acceptable cosmetic outcome was achieved in 48. Two-year actuarial estimates for progression-free survival, disease-free survival, and overall survival were 97.9%, 94.1%, and 87.9%, respectively. There were no deaths attributable to lip cancer. The authors of the study concluded that gold grain interstitial low-dose rate brachytherapy is highly successful in treating patients with squamous cell carcinoma of the lip and preserving patients’ appearance. They also noted that this treatment method is especially useful for patients who are elderly or live in a remote location, and for treating lesions that are small, in previously radiated areas, or treated with prior surgery.

Chemotherapy With or Without Bevacizumab in Treating Patients With Recurrent or Metastatic Head and Neck Cancer 

This clinical trial will test whether combination chemotherapy is more effective in treating patients with recurrent or metastatic head and neck cancer when given with or without the monoclonal antibody bevacizumab. The chemotherapy regimen being tested consists of cisplatin, docetaxel, and fluorouracil. The primary outcome measure of the study will be overall survival. Secondary measures include toxicity, objective response rate, progression-free survival, and impact of comorbidity.

Useful Online Resources and Clinical Trials for Head and Neck Cancers

Net Guides: Head and Neck Cancers

	The search for a screening tool that can help detect lung cancers at early stages has been a focus of research aimed at the leading cause of cancer death in the United States. While much excitement has been created by the performance of helical computed tomography (CT) scans in a large National Cancer Institute (NCI) trial that ended last year, work continues on creating imaging technology that clinicians can use for improved diagnoses.

	VisionGate, Inc is a 10-year-old company that has developed the Cell-CT™ system, which produces 3-dimensional (3D) images of cell samples without the use of x-rays. In September, VisionGate opened a laboratory in Phoenix, Arizona, near 1 of its academic research partners. The company is working on studies needed to support an application with the FDA to bring the technology to market.

	Here, Thomas Neumann, MD, vice president for Medical Sciences at VisionGate, discusses the technology.

Please describe how the Cell-CT technology works.

VisionGate named its instrument the “Cell-CT” because it is used to image cells with techniques that are generally applied in CT. However, the Cell-CT does not work with x-rays; it employs light sources common in standard microscopes. The Cell-CT is used to create high-resolution 3-dimensional (3D) images of cells for the diagnosis of important diseases, such as cancer.

	Briefly, suspensions of cells isolated from human specimens are fl owed through a rotating glass capillary tube smaller than a human hair. One by one, the rotating cells pass by a microscope objective that images each cell from hundreds of different angles. The images are then automatically reconstructed, using CT, into 3D objects of unsurpassed precision, allowing for improved detection of cellular changes specific to certain diseases.

	Analysis can be done through visual examination of the 3D images by a cytologist or cytopathologist, or automatically by using computer programs that are trained to recognize cell features of diagnostic value. Principally, any cellular specimens can be imaged on the Cell-CT. Sputum samples, which contain cells shed from the inner lining of the lungs, are used for lung cancer screening. To produce these specimens, patients are asked to expectorate phlegm (sputum) from their lungs, a collection procedure that is both easy and noninvasive.

Would the Cell-CT replace x-ray CT scans or be used to enhance the results of current technology?

	These 2 imaging techniques are complementary rather than competitive. The Cell-CT can detect cancer cells in sputum, whereas x-ray CT is used to discover suspicious nodules in the lung. The Cell-CT will not replace x-ray CT. Lung cancer usually develops over decades, often as a result of prolonged exposure to carcinogenic substances due to smoking. The features of the epithelial cells that comprise the inner lining of the lungs are indicative of the cancer risk. A larger degree of abnormality in the cells corresponds with an increased likelihood to develop lung cancer in a certain time window. Thus, the Cell-CT is not only trained to detect cancer cells in lung cancer patients, it can also characterize the degree of precancerous changes in cells from at-risk patients. Since the Cell-CT test is noninvasive, economical, and easy, it can be used repeatedly. Cytology is known for very high specificity—ideal for combination with x-ray CT, which is associated with a high false-positive rate. An efficient pretest based on automated sputum cytology would significantly improve the cost effectiveness of x-ray CT.

In what stage of development is the Cell-CT technology?

	The current generation Cell-CT was developed for applications in scientific research and small clinical studies. A number of published studies in the biomedical field have established the superiority of the Cell-CT. Several of our instruments have been purchased by research institutions. We are currently developing the next generation of Cell-CTs that will serve as diagnostic platforms in large-scale laboratories. The new-generation Cell-CT will analyze human specimens automated and with high throughput.

Please discuss the $2.6 million grant the company won from the National Institutes of Health (NIH).

	The NIH has designed a program called Biomedical Research, Development, and Growth to Spur the Acceleration of New Technologies (BRDG-SPAN). This program provides significant financial support for accelerating the market introduction of technologies with the ability to lead to a significant breakthrough in medicine, combined with a significant business potential in United States and/or global markets. The data on Cell-CT performance submitted to the NIH convinced the review panel of the impact of VisionGate’s technology. Other important review criteria were the research and development strategy, and the business plan, as well as the qualification of the team. VisionGate was selected among 10 awardees for this program.

What studies/trials are underway or planned?

	VisionGate has a number of ongoing clinical collaborations on several important diseases, with the main focus on lung cancer. We use sputum specimens from lung cancer patients and noncancer-risk patients to train our system to automatically distinguish between normal cells, cancer cells, and cells that are on the path to becoming cancerous. Additionally, we are storing a large number of sputum specimens to be used in a screening study once the training is completed. The main objective of these trials is to demonstrate high sensitivity and specificity for abnormal cells in sputum.

Which lung cancer patients would most likely benefit from the Cell-CT technology? That is, early or later-stage patients?

	Early-stage lung cancer patients who typically have no symptoms will likely benefit most from the Cell-CT technology. This does not mean that the detection of advanced cancers is unimportant—the treatment options for late- stage cancers are improving. Furthermore, an enormous future potential for the Cell-CT lies in lung cancer prevention. There are already several drugs in clinical trials that promise to reverse the abnormal features in cells of the lung, and to reduce the cancer risk. The Cell-CT would be the ideal technology for selecting the right patients and for monitoring the treatment response in lung cancer prevention therapy.

Explain why VisionGate describes the Cell-CT as platform technology? What other cancers could it analyze?

	The Cell-CT is a platform technology because it enables a range of diagnostic and scientific applications. VisionGate has performed a number of research studies that expanded the capabilities of the Cell-CT beyond lung-cancer. For example, we have imaged clusters of nanometer-size particles incorporated into cells, the 3D-distribution of specific proteins within individual cells, and chromosome sets of the same cells in brightfield and fluorescence mode. In the diagnostic area, we are particularly interested in bladder cancer, esophageal cancer, and oral cancer. We have also developed a Cell-CT-based test for aspiration of gastric contents in conjunction with gastroesophageal reflux disease (GERD). Chronic exposure of small amounts of stomach contents can cause lung conditions, such as chronic cough, asthma, and pulmonary fibrosis. The Cell-CT test measures the uptake of lipids (derived from food particles) in lung macrophages—the cell type responsible for keeping the lung “clean.” The test result can be used to detect aspirators among GERD patients and for monitoring treatment success.

What technological advances make Cell-CT possible?

	Clearly, the many advances in computer technology have enabled us to handle such data-intensive processes as image construction, processing, and analysis. For example, each single cell is digitally imaged in 2D from 500 different angles, and all these images are then tomographically assembled into a virtual 3D space. This computation has to happen very fast in order to achieve reasonable throughput for cell specimens. Other technological advances that have benefited the Cell-CT development are the precision of microfabricated components that are used in our disposable specimen cartridges.

What is VisionGate’s role in the International Early Lung Cancer Action Program (I-ELCAP) and the Biodesign Institute at Arizona State University?

	The I-ELCAP and VisionGate have longstanding collaborations. I-ELCAP-participating sites like the University of Toronto, Swedish Medical Center, and the University of Navarra (Spain) have provided us with sputum specimens from lung cancer patients or high-risk patients to train the Cell-CT and for upcoming screening studies. The Biodesign Institute was the first scientific organization to purchase a Cell-CT system for scientific research. The Biodesign Institute and VisionGate maintain a number of collaborative research studies.

When do you think this product will be ready to submit for FDA approval? When do you think it might reach the market?

	We plan to complete our FDA studies by the end of this year. Market introduction depends on a number of factors, including financial aspects, production capabilities of the manufacturer, and partnering with a large corporation with a footprint in the diagnostic market. VisionGate may need at least 12 months following FDA submission for the regulatory clearance that would allow the company to market the sputum test for lung cancer.

What are the major challenges you and your company have faced thus far in developing this technology? What challenges loom in the future?

	The biggest challenges so far were in the translation of the Cell-CT prototype into a system that fulfills the operational and throughput requirements of a clinical lab. The principles of the Cell-CT technology were established early, and the first generation of Cell-CTs quickly found use in scientific research. Diagnostic platforms, however, have additional requirements, such as high-throughput capabilities, automation, and standardization of specimen collection and preprocessing (fixation, staining, etc). This requires aligning the research and development efforts for hardware, software, and specimen preparation.

	The major challenges lie behind us. We are on a clear path to completing the development of a high-throughput system for VisionGate’s lung-cancer test (LuCED). VisionGate has set an ambitious timeline for bringing the LuCED test to the market, which presents an ongoing challenge.

The search for a screening tool that can help detect lung cancers at early stages has been a focus of research aimed at the leading cause of cancer death in the United States.

Getting a Better Look at Lung Nodules: Cell Scan Delivers Images Without X-rays An Interview With Thomas Neumann, MD

	There’s been a flurry of activity in recent weeks when it comes to oncology drug filings at the FDA. While every application is unique, the agency is required to decide within 60 days whether a new drug application (NDA) will move forward for a full review.

	The FDA’s Center for Drug Evaluation and Research seeks to review an NDA within 10 months at the latest and within 6 months for those applications granted priority status, according to agency policies.

	Here are 5 drugs that have advanced through the clinical trials process to FDA filings since mid-December.

Promising Prostate Cancer Drug Under Review

	Abiraterone acetate, which has generated much excitement in research circles as a treatment for metastatic advanced prostate cancer, was submitted for review under an NDA filing in December. The drug is an oral androgen believed to inhibit the key enzyme CYP17. Centocor Ortho Biotech Inc, Horsham, Pennsylvania, is seeking approval to market the drug for patients with castrate-resistant prostate cancer who have received prior chemotherapy containing a taxane.

	The NDA for crizotinib (PF-02341066), a first-in-class treatment for patients with advanced non-small cell lung cancer (NSCLC), is being submitted on a rolling basis after the FDA granted the drug fast-track status in December, said Pfizer Inc. The company, headquartered in New York City, anticipates completing the submission by July. Crizotinib, an oral compound, is an anaplastic lymphoma kinase (ALK) inhibitor for NSCLC patients whose tumors are ALK-positive.

	Carfilzomib, a next-generation proteasome inhibitor, will be evaluated for approval under the fast-track designation for the treatment of patients with relapsed and refractory multiple myeloma. Onyx Pharmaceuticals, Inc plans to complete its NDA submission on a rolling basis by midyear. The Emeryville, California, company is developing carfilzomib under the orphan drug program. The drug also is being investigated as a first-line multiple myeloma treatment as well as in lymphoma and other cancers.

Approval Sought for New Vinorelbine Formulation

	Exelbine (ANX-530) is under review as a novel emulsion formulation of the chemotherapy drug vinorelbine for the treatment of non-small cell lung cancer. Adventrx Pharmaceuticals, Inc said its formulation is aimed at reducing the incidence and severity of injection-site reactions patients experience with Navelbine, which has been approved since 1994, and its generic equivalents. The San Diego, California, company announced the NDA filing in January and expects the FDA to complete its review by September 1.

	A Norwegian drug development company is recruiting patients for a clinical trial of elacytarabine, a novel lipid-conjugated form of cytarabine for the treatment of patients with acute myeloid leukemia (AML), after the drug was granted fast-track status in December. Clavis Pharma, based in Oslo, said clinical trial results are expected during the second half of 2012, with regulatory filings to follow if findings are positive. Elacytarabine has been designated as an orphan drug by the FDA and the European Medicines Agency, the company said.

	Physicians will be able to make a diagnosis based on what they see on their iPhone or iPad now that the FDA has given its seal of approval to a mobile radiology application for the first time. Mobile MIM, created by MIM Software Inc, enables physicians to analyze radiology images created in a hospital or office and transferred via a secure network to a portable wireless device.

	The FDA said various devices were tested for luminance, image resolution, and noise before the Apple product was chosen. One important Apple feature is an interactive contrast test that allows the user to check the screen so the lighting conditions do not interfere with the ability to see subtle differences in images.

	The FDA cleared the application for viewing images from computed tomography, magnetic resonance imaging, and nuclear medicine technology such as positron emission tomography. The agency said it is indicated for use when physicians are not able to access a workstation. For more information, visit 

	The FDA is reminding healthcare professionals to check labels on prep pads to see whether the product is sterile or nonsterile in the wake of the recall of Triad pads and swabs potentially contaminated with Bacillus cereus, which can cause rashes and skin infections. The Triad pads are sold in retail pharmacies and are packaged in kits with certain injectable drugs. In January, The Triad Group of Hartland, Wisconsin, launched a voluntary recall of all lots of its alcohol prep pads, alcohol swabs, and alcohol swabsticks, including those products marked as sterile as well as nonsterile. The recall covers prep products Triad markets under its own label as well as 8 third-party manufacturers. For further information, check these sites:

	An effort to extend the approved uses of Avodart (dutasteride) for reducing the risk of prostate cancer in men already deemed vulnerable faltered in January. GlaxoSmithKline said the FDA issued a complete response letter on its supplemental new drug application, meaning the approval process cannot move forward in its current form. The decision does not affect any currently approved uses for Avodart. The drug is indicated for treating symptomatic benign prostate hyperplasia (BPH) in men with an enlarged prostate, for reducing the risks of acute urinary retention, and for reducing the need for BPH-related surgery in combination with tamsulosin.

Rituxan Use Extended to Advanced Lymphoma

	Rituxan (rituximab), a therapeutic antibody in use since 1997, is now approved as a first-line maintenance treatment for patients with advanced follicular lymphoma. The FDA based its January 28 decision on the Primary Rituxan and Maintenance (PRIMA) study, which showed that patients who responded to Rituxan plus chemotherapy nearly doubled their likelihood of progression-free survival if they continued on Rituxan therapy every 2 months for 2 years. The drug also is indicated in certain other lymphoma patients and rheumatoid arthritis. Genentech, a member of the Roche Group, is partnering with Biogen Idec in the United States.

Breast Implants Raise Concern of Link With Rare Lymphomas

	The FDA is asking healthcare professionals to report confimed cases of anaplastic large cell lymphoma (ALCL) in women who have received breast implants in order to evaluate the risk the products might pose. Concerns about the association of saline and silicone gel-filled breast implants with ALCL surfaced after about 60 cases were reported worldwide. The numbers, however, have been difficult to verify, the FDA said. From 5 million to 10 million women worldwide have received breast implants. ALCL is a rare cancer diagnosed in about 1 of 500,000 women in the United States annually; it is diagnosed in only about 3 of every 100 million women without implants.

	Consumers have long had their pick of gadgets that help promote healthy lifestyles. Now, a major health insurer is teaming up with an exercise equipment manufacturer to encourage office workers to make the most of their workday by going for a walk at their desks.

	Aetna is offering its employer customers an opportunity to purchase the Details Walkstation at a discount through a partnership with the manufacturer, a division of Steelcase. The station includes a treadmill with a quiet motor and a maximum speed of 2 miles per hour and a desk that can be adjusted to the height of different users, the companies announced jointly in January. The treadmill controller measures speed, time, distance, and calories burned.

	“I spend a lot of time on conference calls and even more time responding to emails and working on reports,” Paul Coppola, an employee in Aetna’s Hartford, Connecticut, headquarters, said in a press release. “When our department was testing the Walkstation, I jumped at the chance to use it. It  was amazing how much more energy I had spending even 30 minutes a day walking and working on the Walkstation.”

Tech Pioneers on Parade at Digital Health Summit

	At the 2011 International Consumer Electronics Show in Las Vegas, Nevada, innovators showcased new technologies that experts are calling “game changers” for digital health. The event’s Digital Health Summit, held January 7, focused exclusively on these technologies and their potential to transform healthcare.

	The highlight of the summit, which was held in partnership with Microsoft, was a panel honoring several companies for advancements in the field. Participating firms  included PhiloMetron, whose digital patch measures how many calories a person has eaten and burned, and Proteus Biomedical, developer of edible microchips that can  be embedded in “smart pills” to provide biofeedback on a medication’s effectiveness.

	The panel also featured a representative from Healthsense, creator of the eNeighbor Resident Monitoring system. The remote system collects vital health data and alerts caregivers to any changes in daily habits, such as sleeping, eating, or bathroom use. It can be customized to a patient’s individual risk profile, and has the potential to help seniors live more independently as they age.

	Rounding out the product offerings was the bebionic, which stood out against some of the more consumer-oriented devices the summit featured. Created by Steeper, this flexible, lifelike bionic hand is backed by powerful software that offers precise motor control through grip patterns that can be customized.

	Through this diverse mix of pioneering products, the panel offered thought leaders a chance to glimpse the future of health technology. “It’s an exciting time, and being able to bring these individuals together in one room to show, talk about, and demonstrate their various technologies is an opportunity I just couldn’t pass up,” said Jill Gilbert, co-producer of the summit.

	December brought the launch of Google’s “Body Browser,” a tool that delivers a 3-dimensional interactive map of the human body. Although the application received mixed reviews for functionality, many health providers agree that it holds promise as a visual aid for patients.

	“Using Body Browser, you can explore different layers of human anatomy by moving the slider to rotate and zoom in on parts you are interested in,” Google wrote in an introduction. Users can search the map through anatomical terms and share the image they’re viewing by copying and pasting a URL.

	The product is currently housed in Google Labs, which means it’s still in the experimental stages. To try the demo tool and provide Google with feedback on how to improve it, visit 

	How long would it take you to run up the stairs of 1 of the world’s tallest buildings? Thomas Dold of Germany scaled 86 flights of steps to the public observation deck—1050 feet in the air&mdash;in 10 minutes, 10 seconds to lead the field in the February 1 Empire State Building Run-Up race while Alice McNamara of Australia beat all women contestants with a time of 13 minutes, 3 seconds. The big winner, though, was cancer research. The Multiple Myeloma Research Foundation, partnering with the New York Road Runners to sponsor the 34th annual event, raised more than $250,000 through the race.

There's been a flurry of activity in recent weeks when it comes to oncology drug filings at the FDA. While every application is unique, the agency is required to decide within 60 days whether a new drug application (NDA) will move forward for a full review.

Priming the Pipeline: 5 New Drugs in Works

	The Internet has been employed in a variety of interesting ways to foster clinical or research agendas. From epidemiological studies to consumer-focused patient decision-support initiatives, individual groups and organizations have attempted to take full advantage of the extraordinary reach and diversity of this powerful and widely used technology.

	A recent report in the gynecologic cancer literature provides an excellent example of the truly unique utility of Internet-based communication to gather remarkably informative data and at the same time serve a vitally relevant educational and quality-improvement function (

. 2010; 119:53-59). Further, the study itself raises provocative questions regarding how such technology might be utilized in the future to optimally manage patients with rare malignant conditions.

	In this initiative, investigators in France interested in the management of uncommon ovarian tumors (ie, germ cell and ovarian stromal cancers) established in early 2002 a Website (

) focused on these specific clinical entities. Ray-Coquard et al had several reasons for embarking on this effort, including the collection of tumor specimens for further analysis, the development of clinical trials focused on the treatment of these cancers, and the relaying of information regarding disease management. It is relevant to note that the ultimate goal of the project was to optimize the care of women in France with these specific malignancies where it was anticipated the overall experience of clinicians outside major cancer centers would be very limited.

	In this analysis, the researchers found that central review of tumor samples by pathology experts resulted in a modified diagnosis in 37% of patients who were eligible for a second opinion (28 of 77 patients). Further, stated disease management in many cases of these uncommon tumors differed from what the specialist gynecologic cancer community might have suggested, at least based on available medical documentation.

	These observations related to histology and specific treatment are of interest and potential concern, and suggest both the need for follow-up of the treated populations to see whether outcomes (efficacy and toxicity) were influenced by the differing opinions on pathology and disease management. One can easily envision specific scenarios where Internet-based strategies could be employed to both obtain objective data and also serve as an educational tool to assist in the optimization of disease management.

	Clinical data obtained through this novel mechanism in the initial 100 patients permitted a global assessment of characteristics of the French population with these malignancies and their outcomes. For example, the research found the median age of the entire study population at diagnosis was 42, with a 5-year overall survival of 94%, and a median progression-free survival of 62 months. Approximately one-half of the population received chemotherapy.

	In the discussion of the very interesting paper, the researchers ask the provocative and complex question of whether the optimal use of Web-based communication designed to improve the outcome of patients with rare cancers should be focused on providing information to less-specialized community-based practitioners that may permit such provider/hospital groups to render more appropriate care locally. Or, they ask, should the major aim be to define patient populations where specialty-based

	care is indicated and utilize the Internet to encourage referrals? Clearly, this issue will be discussed many times in the future and it is likely that, depending upon specific circumstances (eg, availability of specialty surgical care or blood component support in the community setting), there will be differing answers to the question.

	We can anticipate that the clinical cancer research community will continue to explore innovative uses for the Internet to enhance communication between interested colleagues and with specific cancer patient populations. The goal will be to improve the ultimate outcome, both survival and quality of life, for patients with a malignancy. As far as this specific French experience is concerned, this initial effort has been considered a success in an internal review, leading the French National Cancer Institute to explore the utility of this approach for other rare tumors.

The Internet has been employed in a variety of interesting ways to foster clinical or research agendas.

From the Editor: Internet Analysis Raises Questions in Rare Cancer Care

National Guideline  Clearinghouse Includes Thrombocytopenia Entry

	The National Guideline Clearing House is a Website run by the Agency for Healthcare Research and Quality, the health services research arm of the US Department of Health and Human Services. The site contains recommendations for the clinical management of many diseases and conditions, including thrombocytopenia. The “Guideline Summary” page for thrombocytopenia begins with the scope and methodology of the guidelines before listing the recommendations, the evidence supporting them, the potential benefits and harms of implementing them, and information on their source. The “Recommendations” section discusses the clinical approach to and basic rules about thrombocytopenia. It then covers the causes of thrombocytopenia (including reasons for decreased production and increased consumption), as well as the clinical approach to treating symptomless patients with various platelet counts, and patients with bleeding and idiopathic thrombocytopenic purpura.

http://guideline.gov/content.aspx?id=11048&search=Prednisolone

Cancer.Net Article Puts Focus on Side Effect

	Cancer.Net is a Website hosted by the American Society of Clinical Oncology. The site is meant to serve as a resource for patients with cancer by providing information that has been reviewed and approved by a board of oncologists. An article on thrombocytopenia can be found on the website that discusses its definition, causes, signs and  symptoms, diagnosis and treatments, and factors that patients with thrombocytopenia should consider. At the bottom of the article are links to other articles that patients with thrombocytopenia may find useful, which cover bleeding and clotting problems, managing side effects, and understanding blood test results. Cancer.Net also has a large number of cancer-related articles that, while not directly related to thrombocytopenia, may be helpful to patients. Articles are sorted in a range of categories, including cancer types, information for the newly diagnosed, risk factors and prevention, genetics, treatment, clinical trials, managing cost, coping, and survivorship. Visitors may also view Cancer.Net’s medical illustrations gallery, collection of medical dictionary resources, and library of publications. Cancer. Net is available in both English and Spanish.

Dose Escalation Study of An antithrombocytopenic Agent in Patients With Chemotherapy-Induced Thrombocytopenia

Levin RD, Daehler M, Grutsch JF, Hall JL, Gupta D, Lis CG

Preclinical studies have shown that small-chain RNA fragments can accelerate platelet recovery in animals that have been exposed to high doses of  chemotherapeutic drugs. There are also anecdotal data supporting that small-chain RNA fragments may have the same use in humans. The purpose of this study was to determine the effect of administering small-chain RNA fragments on platelet recovery in patients with chemotherapy-induced thrombocytopenia (CIT). The study required patients to have solid tumors and post-chemotherapy thrombocytopenia with a nadir of < 80,000 platelets/ml, but made no exclusions based on Eastern Cooperative Oncology Group status, tumor type, tumor burden, or chemotherapeutic agents. Patients were given unique preparations of RNA derived from either E coli or yeast, which were self administered sublingually every other day while undergoing chemotherapy treatment. Ten patients per group received 20, 40, or 60 mg as a starting dose. Dosage was increased by 20 mg at the start of each cycle to a maximum dose of 80 mg as long as the nadir remained <80,000 platelets/ml. Patients would then continue taking the maximum dose for 3 cycles of chemotherapy. Participants in the study were required to keep a diary of RNA fragment and magnesium administration, as well as any side effects experienced.

Of the 2 groups, patients receiving the E coli RNA fragments showed a faster recovery in platelet count and higher nadir platelet count. In addition, none of the patients receiving E coli RNA fragments needed a chemotherapy dose reduction due to CIT. Patients receiving yeast RNA fragments required chemotherapy dose reductions due to grades 3 and 4 CIT. The authors concluded that patients undergoing myelosuppressive chemotherapy demonstrated an improvement in platelet nadir and recovery time when receiving concurrent E coli RNA fragments as compared with patients receiving yeast RNA fragments, and that 60 and 80 mg doses of E coli RNA accelerated platelet recovery, with 80 mg being the optimal dose for minimizing CIT. The authors also noted that further clinical investigation is needed to establish the benefits of E coli RNA fragments in the management of CIT.

http://www.ncbi.nlm.nih.gov/pubmed/20955619

Safety/Efficacy Study of a Drug to Reduce Rhrombocytopenia

in Patients Receiving Chemotherapy for Ovarian, Fallopian Tube, or Peritoneal Cancer

This study will test the safety and efficacy of 2 different dose levels of a new experimental drug called TXA127, also known as angiotensin 1-7, in the management of CIT. The study will focus specifically on CIT caused by chemotherapy regimens of gemcitabine and carboplatin or gemcitabine and cisplatin for the treatment of ovarian, fallopian tube, or peritoneal cancer. There will be 3 arms to the study, with patients receiving either 100 ug/kg/day of TXA127, 300 ug/kg/day of TXA127, or placebo. The primary outcome measure of the study will be the severity and incidence of thrombocytopenia as determined by the number of patient chemotherapy cycles during which the platelet count is below 50,000/mm3. Secondary outcome measures will be the severity and incidence of thrombocytopenia as determined by the number of patients who experience a platelet count below 50,000/mm3, and as determined by absolute nadir and time to platelet count recovery for each cycle and study subject; the frequency and severity of serious adverse events; and the incidence and grade of toxicity experienced by each dose group.

Useful Online Resources and Clinical Trials for Thrombocytopenia Supportive Care

Net Guides: Thrombocytopenia Supportive Care

Principles and Practice of Gastrointestinal Oncology —Second Edition

Kelsen DP, Daly JM, Kern SE, Levin B, Tepper J

	This textbook covers interdisciplinary aspects of the characteristics and management of gastrointestinal cancers. Topics include the molecular biology, diagnosis, pathology, surgical and radiation treatment, and palliative care for these cancers. There are also chapters on radiation oncology, cancer genetics, and medical oncology, as well as esophageal, gastric, pancreatic, hepatocellular, biliary tree, and colorectal cancers. Another section focuses on uncommon cancers, such as neuroendocrine tumors and small-bowel cancers. For each cancer site, the book covers the disease’s epidemiology, screening, prevention, molecular biology, genetics, pathology, anatomy, staging, and clinical management. This textbook serves as a useful reference for anyone involved in the research or management of gastrointestinal cancers.

	The Liver Cancer Network (LCN) is a Website that is part of the Allegheny General Hospital Liver Program in Pittsburgh, Pennsylvania, which is dedicated to treating liver cancer and educating patients with liver cancer and their loved ones. The information is divided into 3 major areas: general liver cancer information, diagnosis, and treatments. The general information section focuses on 3 topics. The first is how the liver works, and it gives brief summaries of the liver, its anatomy, its digestive function, and its circulatory function. The next topic covers liver cancer itself, and it offers an explanation of cancer in general, liver cancer specifically, carcinogenesis, and cancer growth. The final topic in this section deals with the symptoms and detection of liver cancer. A number of colored diagrams and illustrations accompany the information. All sections contain underlined terms that are linked directly to their definitions in the LCN’s glossary. The section on diagnosis explains liver cancer staging and the various tests used to diagnose and stage liver cancer, including physical exams, blood tests, chest x-rays, computed tomography (CT) scans, CT angiograms, ultrasounds, magnetic resonance imaging, colonoscopy, laparoscopy, and liver biopsy. Several examples of imaging techniques are included. The final section discusses treatments for liver cancer, specifically surgery, chemotherapy, chemoembolization, radiation therapy, radiofrequency ablation, and liver transplantation. A page on yttrium-90 internal radiation is under development. This section also features photographs and diagrams.

	This CME activity features a panel of experts discussing the results of the latest clinical trials concerning gastrointestinal cancers. The discussion is shown via a Webcast with audio that is accompanied by a slideshow containing charts and key points that are being discussed. These slides may be downloaded separately. The gastrointestinal malignancies focused on in this CME are pancreatic cancer, hepatocellular carcinoma, colorectal cancer, and gastric and esophageal cancer. For each disease, the speakers highlight findings from recent clinical trials presented at the 2010 Gastrointestinal Cancers Symposium and the American Society of Clinical Oncology (ASCO) 2010 Annual Meeting, and discuss how those findings likely will impact clinical management of the disease in the future. After completing this activity, participants will be able to summarize data from the symposium and ASCO meeting, describe the results of clinical studies testing emerging therapies for pancreatic and hepatocellular cancer, the role of biomarkers in selecting therapies for patients with colorectal cancer, and new biologic therapies and cytotoxic chemotherapy regimens being tested for colorectal cancer. Participants will also be made aware of new surgical and pharmacologic approaches to the treatment of gastroesophageal cancers, as well as how genetic and molecular markers may be used in those treatment methods.

Laparoscopy-Assisted Gastrectomy in Patients With Previous Endoscopic Resection for Early Gastric Cancer

The purpose of this retrospective analysis was to determine whether endoscopic resection in patients with early gastric cancer has an impact on subsequent laparoscopy-assisted gastrectomy (LAG), and what that impact might be. The study included 711 patients who underwent LAG, 111 of whom had previously undergone endoscopic resection. The researchers then compared patient characteristics, operative outcomes, and postoperative outcomes between the 2 groups. They also analyzed risk factors associated with postoperative complications. 

 There were no significant differences in procedure duration or blood loss between the 2 groups. The group that had previously undergone endoscopic resection had fewer dissected lymph nodes and a lower rate of preservation of the celiac branch of the vagus nerve, especially in patients who underwent LAG within 2 months following endoscopic resection. The study found no significant differences in early postoperative outcomes, including complications, gastrointestinal recovery, and postoperative hospital stay length. The researchers concluded that LAG may be safely performed in patients who have already undergone endoscopic resection, though it may make the LAG procedure more difficult. They also concluded that it has little influence on early postoperative outcome.

RAD001 and AV-951 in Patients With Refractory, Metastatic Colorectal Cancer 

This clinical trial will test the use of 2 antiangiogenic agents in the treatment of metastatic or refractory colorectal cancer. The agents being tested are AV-951, a vascular endothelial growth factor inhibitor, and RAD001, an mTOR inhibitor. The primary outcome measures of the test are the safety, tolerability, and maximally tolerated dose of RAD001 and AV-951 in combination, as well as the progression-free survival at the maximally tolerated dose. Secondary outcome measures include overall survival and tumor response rate.

Useful Online Resources and Clinical Trials for Gastrointestinal Cancers

Net Guides: Gastrointestinal Cancers

American Society of Pediatric Hematology/Oncology

	The American Society of Pediatric Hematology/Oncology (ASPHO) is a multidisciplinary organization that works to promote the care of children and adolescents with blood disorders and cancer through the advancement of research, professional education, treatment, and clinical practice. For a regular fee, physicians can become a member of  ASPHO. Membership grants a number of benefits, including a bimonthly e-newsletter; monthly issues of 

, the official journal of ASPHO; and a discount on the registration fee for ASPHO’s annual meeting. Members can take ASPHO’s review course for physicians planning to take the American Board of Pediatrics (ABP) examination for initial certification in pediatric hematology/oncology or Part III of the ABP’s Program for Maintenance of Certification in the Pediatric Subspecialties. An online review course features 22 hour-long lectures with slideshows prepared by experts in the field. Membership also grants access to ASPHO’s online member community tools, which enable members to locate and communicate with one another, share information and documents in a searchable library, participate in  discussions, and view or create blogs.

Pediatric Low Grade Astrocytoma Foundation

	The Pediatric Low Grade Astrocytoma (PLGA) Foundation is a nonprofit organization dedicated to helping children with PLGAs and their families through information and support. The PLGA Foundation Website has a section with information on PLGAs that covers what PLGAs are, other types of brain tumors, brain tumor locations, newly diagnosed patients, chemotherapy, radiation therapy, treatment complications, clinical trials, and common questions patients may have. This part of the site also features a video gallery with Webcasts that are both educational and inspirational. The “Resources” section helps patients and their families find support groups, information on children’s specialists and programs, financial support, and other useful sites. A community section includes a parent support network, a news center, a calendar of upcoming events, inspirational stories, and more.

Ultrasound Biomicroscopy in the Management of Retinoblastoma

	This CME activity is based on a study that evaluated the role of ultrasound biomicroscopy (UBM) in the management of children with retinoblastoma. The study reviewed the clinical records of children who were diagnosed with retinoblastoma at the Hospital for Sick Children in Toronto, Canada, from January 1995 to December 2007, for whom UBM was used to determine the extent of the intraocular tumor. Pathological correlation was then performed for enucleated eyes. For all of the enucleated eyes included in the final analysis, UBM did not yield any false-negative or false-positive results. The authors concluded that UBM provided a sensitive and reproducible visualization of the ciliary region, anterior segment, and anterior retina, enabling more accurate staging of the advanced disease process, which is vital for optimal management. On completing this CME activity, participants should have an understanding of the prognosis of retinoblastoma and the current imaging techniques that can inform prognosis. Participants should also be able to describe the sensitivity and specificity of ultrasound biomicroscopy in the detection of retinoblastoma’s anterior extension.

Definitive Radiotherapy for Unresectable Pediatric and Young Adult Nonrhabdomyosarcoma Soft Tissue Sarcoma

Smith KB, Indelicato DJ, Knapik JA, et al

The purpose of this study was to evaluate the prognostic factors, outcomes, and complications in pediatric and young adult (age ≤30 years) patients with nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) who were treated at the University of Florida from 1973 to 2002. The study included 19 patients who were diagnosed with NRSTS and treated with radiotherapy after biopsy, 13 of whom had high-grade tumors. Median patient age at the time of radiotherapy treatment was 19.6 years, and median dose was 55.2 Gy. Twelve patients underwent chemotherapy. Prognostic factors for local recurrence, distant metastases, and survival were analyzed. 

The median follow-up was 2.6 years, and the 5-year local-control rate was 40%. Nine out of 13 local failures occurred in the absence of metastatic disease, and all patients with local failures died of their disease. Eight patients died without evidence of distant metastases. A total of 14 patients died of their cancer. Low/intermediate-grade tumors tended to have improved local control. The rates of freedom from distant metastases and overall survival at 5 years were 68% and 37%, respectively. There was 1 grade 4 complication. The authors concluded that pediatric and young adult patients with unresectable NRSTS have a poor prognosis, and that study efforts focusing on treatment intensification are justified. The authors also noted that because all patients with local recurrence died of the disease and a majority of those deaths occurred without distant spread, improving local control might improve survival.

Combination Chemotherapy and Surgery in Treating Young Patients With Wilms Tumor

This study will test the efficacy of combination chemotherapy with surgery in the treatment of young patients with Wilms tumor. The chemotherapy regimen  consists of carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide phosphate, and vincristine sulfate. It will be administered before surgery to shrink the tumor and reduce the amount of healthy tissue that needs to be removed, as well as after surgery to kill any remaining tumor cells.

Useful Online Resources and Clinical Trials for Childhood-Tumors

Net Guides: Childhood Tumors

	The Society for Neuro-Oncology (SNO) describes itself as “a multidisciplinary organization dedicated to promoting advances in neuro-oncology through research and education.” The SNO Website has a resources section for medical professionals, which includes research grants, a literature and book review section, a career center for both job seekers and employers, an organization directory, a collection of useful links, and other resources for patients. This section contains information on SNO’s international outreach research fellowship program, as well as the institutions that have agreed to be potential hosts for it. The SNO Website features a news area with the latest articles, press releases, upcoming events, and a spot to sign up for the SNO e-newsletter. For a yearly fee, professionals may subscribe for either a full or associate membership with SNO, depending on whether they have a doctorate-level degree. Those undergoing scientific or clinical training may also sign up for a trainee  membership at a lower fee. SNO members receive monthly issues of SNO’s offi cial journal, Neuro-Oncology, as well as discounts for the annual SNO Scientific Meeting and Education Day, e-blasts and neuro-oncology news, and access to the members-only section of the Website.

	The Northwestern Brain Tumor Institute (NBTI) is run by a multidisciplinary team of medical experts from the Robert H. Lurie Comprehensive Cancer Center and the Feinberg School of Medicine at Northwestern University, as well as the Northwestern Memorial Hospital. The NBTI is dedicated to treating patients with brain tumors, researching a cure, and providing patients with the information and resources. Patients can find information on the symptoms, diagnosis, types, and treatment options for brain tumors. The “Diagnosis” section describes all of the tests and imaging techniques used to diagnose a brain tumor, while the “Treatment” section offers brief descriptions of neurosurgical treatment, radiation therapy, and other available therapies. The “Types of Brain Tumors” section lists all the various brain tumor types, sorted into gliomas and nongliomas, and clicking on any of the types will bring up a window describing the tumor and where it occurs. Other resources offered by the NBTI include downloadable audio lectures, a glossary of terms, a newsroom, and a page with links to the Websites of other helpful organizations.

www.braintumorinstitute.org/home/index.cfm

Current Perspectives in Adult Glioblastoma

	This CME activity focuses on emerging data concerning the diagnosis and treatment of glioblastoma in adults. The activity consists of a slideshow presentation with audio or viewable transcripts followed by a test on the material. The slideshow contains various charts, graphs, tables, and other information being discussed by the expert giving the presentation. On completing this activity, participants should have a full understanding of the diagnostic assessment of glioblastoma and the disease’s treatments,  including surgery, radiation therapy, and chemotherapy. Participants should also be able to describe obstacles in treating recurrent glioblastoma and glioblastoma in special patient populations, as well as emerging treatment methods that have shown promising results for improving outcomes in adults with the disease. 

Notch1 Is an Independent Prognostic Factor for Patients With Glioma 

Li J, Cui Y, Gao G, Zhao H, Zhang H, Wang X

Notch signaling has been shown to affect cell proliferation, differentiation, and apoptosis in both positive and negative ways (depending on cell type) in  malignancies. This study sought to evaluate the levels of Notch1 protein expression in gliomas in order to determine whether Notch1 expression was associated with glioma survival rates. For the study, the researchers collected gliomas from 274 patients who had not undergone chemotherapy, then assessed the expression of Notch1 protein by immunochemistry assays. They then analyzed the staining evaluation results statistically in relation to a number of clinicopathological characteristics. The associations of Notch1 expression with glioma prognosis were assessed using Kaplan-Meier and Cox proportional hazards regression models. 

 The study found elevated expression levels of Notch1 in gliomas compared with control normal brain tissue. It also found that Notch1 expression was closely associated with glioma progression, as expression levels increased from grades I to IV glioma. Patients with Notch1 positive gliomas had a significantly lower overall survival rate than patients with Notch1 negative tumors, and multivariate analysis showed that Notch1 was an independent prognostic factor for patients with glioma. The authors concluded that Notch1 is upregulated in glioma and related to tumor progression. They also noted that Notch1 could serve as a novel prognostic marker that is independent of, and additive to, the World Health Organization grade. 

Safety Study of Intracerebral Topotecan for Recurrent Brain Tumors 

This clinical trial will test the chemotherapy drug topotecan in the treatment of recurrent brain tumors using a novel drug delivery strategy called intracerebral clysis (convectionenhanced delivery). Intracerebral clysis uses a microinfusion pump to establish a pressure gradient in the brain using catheters implanted in the tumor and  surrounding tissue. This gradient creates convective forces that distribute a therapeutic agent throughout the tumor and surrounding tumor bed. The primary outcome  measures of the study include progression-free survival, overall survival, and grade 3 adverse events.

Useful Online Resources and Clinical Trials for Brain Cancer

Net-Guides: Brain Cancers

Gene Signature Test Predicts Colorectal Cancer Recurrence

ColoPrint, a microarray-based gene signature test, accurately identifi ed the risk of recurrence of colorectal cancer in patients with localized stage II disease, raising the potential of an exciting new prognostic tool for clinicians.

February 2011 | Oncology Live®