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 states that approximately 20,000 American women receive an ovarian cancer diagnosis annually, with about 15,000 dying of the 

. This high fatality rate is attributable to vague or absent premalignant signs and symptoms early in the disease and screening methods that often fail to detect early stage cancer.

Jacques Abramowicz, MD, director of obstetrical and gynecological ultrasound at Rush University Medical Center in Chicago, explains that if physicians are able to catch ovarian cancer during stage I, the 5-year survival rate is greater than 90%. Unfortunately, between 60% and 70% of ovarian cancers are not diagnosed until stage III or IV, where the survival rate drops to as low as 10%.

“When you do a pap smear and find some changes in the cells, that’s a potential sign for future cancer, and we can do something about it,” Abramowicz says. “We don’t have something like that in the ovaries. And you can tell a woman to examine her breasts every month, but you can’t do that for the ovaries.”

Testing for CA-125 levels in the bloodstream has been considered the gold standard for ovarian cancer screening in recent years. While this test may be able to detect epithelial ovarian cancer, the most common form of the disease, the test is nonspecific. According to Abramowicz, CA-125 can be found in many tissues, including the uterus and around the lungs. In addition, many conditions are known to increase CA-125 levels, such as endometriosis, and even normal menstruation; thus, it is not the most useful biomarker.

Combining ultrasonography with the CA-125 blood test offers some improved screening results, but not for early stage disease. For example, the results of a study published in the April issue of 

 found that while 60 of 89 cancers were diagnosed using this screening modality, 72% of these cancers were detected at an advanced stage. The study also found that screening often leads to unnecessary biopsies and other surgical procedures. “There’s a certain number of surgeries which are considered acceptable in order to find one cancer,” Abramowicz says. “If we do 10 surgeries and find one cancer, we’re sort of willing to accept that number.” The aforementioned study found a surgery-to-cancer ratio of 19.5:1. According to Abramowicz, “That’s very high. You want a screening test to be good enough so you don’t need to do too many unnecessary surgeries.”

Despite the limitations of screening for ovarian cancer using a combination of CA-125 levels and ultrasonography, this screening method can save lives. Jennifer Fox, director of marketing and communications for OrthoIndy and the Indiana Orthopaedic Hospital in Indianapolis, is an ovarian cancer survivor who recently celebrated her 5-year anniversary of being cancer-free, and she credits ultrasonography for helping to catch her stage I cancer.

“For about 10 years, I had a lot of bladder issues—urinary tract infections, kidney infections&mdash;and it got to the point where I was having them twice a month,” Fox says. “I was on a lot of antibiotics, and I became allergic to many of them.” Eventually, an ultrasound revealed that a 7-lb tumor had engulfed one ovary. The tumor was located above Fox’s bladder, promoting bacteria build-up, which resulted in the repeated infections. A subsequent blood test revealed high CA-125 levels, indicating the likelihood that the tumor was cancerous, and surgery was performed.

“From oncologists I’ve spoken with, it was pretty outstanding that they found [the cancer] when they did,” Fox says. “I know insurance companies don’t want to be giving ultrasounds to everyone. But if women are presenting with certain issues, I think it’s such a small price to pay. The fact that I had one probably saved my life.”

Several efforts are currently underway to improve early screening for ovarian cancer. Results of a 

 published in Gynecologic Oncology found that the combination of Fujirebio Diagnostics blood tests for HE4 and CA-125 were able to identify patients who were at high or low risk for developing ovarian cancer (http://tinyurl.com/nytwpn). The HE4 assay was recently cleared by the FDA as an aid for monitoring recurrence of epithelial ovarian cancer, and it is thought that combining the HE4 and CA-125 tests may enable physicians to preoperatively identify those patients with a high risk of malignancy. This protocol is currently being reviewed by the FDA.

, a biotechnology company, is making progress in developing monoclonal antibodies (MAbs) for the detection of cancer at an 

. MAbs bind to antigens on the surfaces of cancer cells. “Cancer cells partly shed these antigens into the blood stream,” explains Amnon Gonenne, MD, CEO of MabCure. “We’re looking for these circulating antigens. We want to come up with a test so when a woman goes for a pap smear once a year, she can have a vile of blood taken and analyzed for the presence or absence of these antigens, which are recognized by our antibody.” The company is planning to begin its first full-scale clinical study of 150 patients at high risk for ovarian cancer. According to Gonenne, the objective of the study is to demonstrate “the potency of our MAbs in detecting [ovarian cancer] in a larger patient population and selecting those MAbs with the highest specificity and sensitivity. These MAbs will become the ultimate candidates for the early diagnosis of [ovarian cancer]. The initial draft protocol and budget have been approved, and we are presently working on the final protocol and associated documents required by the hospital Institutional Review Board.”

While ovarian cancer screenings using CA-125 measures and ultrasonography are limited and generally fail to fi nd cancer at an early stage, this protocol can save lives. In the near future, more sensitive and specific diagnostics may become available, as several companies are working on identifying biomarkers that will better determine ovarian cancer risk.  

Articles

The Ovarian Cancer National Alliance states that approximately 20,000 American women receive an ovarian cancer diagnosis annually, with about 15,000 dying of the disease.

Ovarian Cancer Screening Focuses on Improving Early Detection

	Electronic communication technologies have radically changed our world, transforming almost every aspect of our daily lives. Most of the tasks we need to perform can be handled electronically, from paying bills and shopping to communicating with friends and family. Although cell phones and the Internet already allow a vast quantity of data to be shared almost instantaneously between individuals, the electronic communications sector shows no signs of slowing down. New options for communication and data storage continue to be developed and are quickly changing how business is conducted; however, there are several areas relevant to health and education that have not moved as rapidly along the evolutionary track from paper to electronic, one of which is medical and textbook publishing. In fact, electronic books (also known as e-books) in general have not taken off as much as one would expect. So, why is this?

	The public, particularly in the United States, increasingly receives its news from electronic media. It may be provided by traditional sources, such as newspapers or television stations that post their standard content online, or alternative methods, such as blogs, Twitter, and forums. Because of the abundance of timely information online, people are less prone to buying newspapers, magazines, and journals, but they still like to buy books. A number of explanations have been advanced to explain why e-books have so far failed to actively capture both the imagination and pocketbook of a public that appears to otherwise eagerly embrace technological advances in communication. Let us examine some of the key reasons:

	• Printed books are easy to access whenever desired and they do not require batteries or charging.

	• Printed books can be easily shared between individuals.

	• Printed books are easy to skim through to find a section of interest

	Printed books represent a tangible possession and form the basis for a visible personal library.

	• Printed books can be obtained free from a local library or relatively inexpensively when bought used.

	• Printed books do not require the expense associated with purchasing a device to display an e-book, which can be costly. Further, these expensive devices will no doubt require replacement at some undefined point in time.

	• Printed books permit the display of a wide variety of images (eg, complex figures and pictures), which may be more difficult to duplicate on an electronic device, and as of yet can not be duplicated in color. Currently, all e-book readers display only in shades of gray, featuring between four (lower-end models) and 16 shades. 

Barriers to the adoption of electronic textbooks 

	While it is not difficult to envision a simple book, such as a novel that consists solely of written words, to be converted to a digital screen, it is something quite different to visualize how e-books could replace textbooks. After all, textbooks are intended to explain complex concepts with both words and images, with most containing countless pictures, figures, graphs, and tables; thus, displaying this information in a way that allows easy navigation between the words and images is imperative. Certain images are also best presented in color, such as histopathology images, and these could only be shown in shades of gray on current readers.

	When it comes to textbooks, size matters. Many e-book readers have a display area that is the size of a paperback, so while they may be great for reading the latest mystery novel, they are not ideal for viewing scientific or medical textbooks; however, there are several e-book readers coming to the market that boast a larger digital display, and we will get into that later.

	Another relevant consideration is the ability to share material across devices with different operating systems. The inability to easily share scientific materials when produced in an electronic format is a barrier that would hamper interchanges between investigators and clinicians and negatively impact how educational activities are conducted. Imagine reading something you believe to be important, and wanting to share it with a colleague, but being unable to do so because he or she does not have an e-book or owns a device made by a competing company with a non- compatible operating system? This situation is reminiscent of that faced by programmers in the early development of personal computers (Microsoft versus Apple), but has been largely resolved. Fortunately, progress is also being made on the e-book front, and several e-reader manufacturers have switched to the EPUB standard, including Sony, Plastic Logic (not yet released), and others.

	Readers, especially those of medical texts and other technical materials, need to have the ability to make annotations in the “book’s margins” for future reference. Most e-book readers now offer this feature. For example, Amazon’s Kindle

 has a QWERTY keyboard—the most used modern-day keyboard layout on English-language computers&mdash;which allows annotations to be added to the text, and because these notes are digital, they can be edited, deleted, and exported. You can also search for terms within the book, so you no longer need to spend time flipping through pages to find what you are looking for, which may also facilitate annotation of text.

The future of e-books in education and medicine 

	Despite some of the concerns regarding e-books, a number of factors provide strong support for envisioning a generally bright future for this format, including in education and the medical sciences. Let us examine some of these factors:

	• There has been a substantial reduction in the cost of e-book readers, making them accessible to more people.

	• The cost of standard print textbooks provides a solid argument in favor of e-book publication. A 

 from the National Association of College Stores noted that the average college student spent approximately $700 on books during the 2007 to 2008 academic year and it is anticipated that these costs will be substantially greater in future years because of increased costs of paper, printing, and distribution.

	• There have been substantial increases in the quantity of material to be presented in educational texts, and 1000+ page books are common for the sciences and medicine. These books are expensive and can be cumbersome to carry around compared with e-books, which are light, portable, and can store numerous textbooks and other materials.

	• E-books are more easily updated and distributed. Information in medicine, especially in oncology, is changing on a daily basis, making many medical texts outdated before they even hit the bookshelf. For 

, the electronic edition of a basic oncology textbook could be updated to reflect the latest data that indicate that patients with metastatic colon cancer and a KRAS mutation should not be treated with an epidermal growth-factor receptor inhibitor. This is important information that may be missing from many newer oncology textbooks because they went to press before this recommendation was made.

	• The availability of nonfiction titles, such as medical textbooks, is increasing. Further, some publishers are testing programs that

	would allow individual chapters of certain books to be bought electronically, rather than the entire e-book.

	• E-books allow for widespread international dissemination of educational and scientific materials to geographic locations with limited access to printed books and journals.

	A number of e-book products are already available and more will be introduced over the next several years, indicating this market is heating up and competition will become fierce. Currently, Amazon’s Kindle is the most popular e-book reader in the United States, and Amazon recently added a 9.7-inch e-book device, called the Kindle-DX, to its existing product line to enhance the reading of material contained in textbooks. A number of academic institutions are piloting this larger e-book reader to assess its potential in this setting. The only e-book readers that now feature a larger screen are the Digital Reader 1000S and Digital Reader 1000SW by iRex Technologies, both of which have a 10.2-inch display. 

 currently boasts over 350,000 titles, and more than 7,000 of them are free. While most of the free e-books are classics available in the public domain, Amazon occasionally offers newer books for free, though these are only available for a limited time.

	Barnes & Noble also recently announced that it has launched its own digital bookstore, and that its customers will be able to access the service’s digital books via multiple platforms, including the iPhone, iPod Touch, and BlackBerry smartphones. Additionally, Barnes & Noble will be the exclusive digital-book supplier for the upcoming Plastic Logic eReader, which they hope will be a strong competitor of Amazon’s Kindle. Since the Plastic Logic eReader has not yet been released, its specs are not yet fully known, but it is expected to measure 8.5 by 11 inches and to be thinner than a pad of paper. It is also reported that the Plastic Logic reader will support Microsoft Word, Excel, Powerpoint, Adobe PDFs, newspapers, periodicals, and books.

	Another large player in the e-book arena is Sony, which is especially; popular in Europe and Asia; however, like Barnes & Noble, Sony is looking to cut into Amazon’s Kindle business. On August 25, 2009, Sony held a press event at the New York Public Library on Fifth Avenue, during which it unveiled three new products: a $199 “Pocket Edition” Reader; a $299 “Touch Edition” Reader; and a $399 “Reader Daily Edition,” which is a wireless 

 with 3G connectivity. One of the most notable features introduced was the support of electronic lending. Users of Sony Readers will be able to download a borrowed book from their brick-and-mortar library and transfer them to their reader for 21 days, after which the fi le will expire; thus, no more fears of incurring late fees because a book is not turned in on time. It is anticipated that eventually readers will also be able to “check out” e-books from their libraries electronically. Because electronic lending is still a fairly new concept, it may prove difficult to find a participating library, but Sony is helping individuals make that search easier. It has partnered with Overdrive.com, a digital media services company, to develop the 

. Simply put in your zip code or state and the finder will pull up a list of libraries that support e-lending in your state or area. Another notable development, as mentioned previously, is that Sony has now switched to the EPUB standard from its former proprietary BBeB format. This move will allow the Sony Reader to work with files purchased from BooksOnBoard.com, NetGalley.com, Powells.com, and any other retailer that adopts the Adobe-backed standard. In addition, Sony Readers will have access to more than one million public domain 

	Another leader in electronics, Samsung, is starting to look at capturing a share of the e-book market and has recently announced its plans to release an e-reader called Papyrus. It is unclear when the device, which is anticipated to cost around $300, may be released in the United States, but it will face some stiff competition. What may distinguish this device from others is its PDA-like quality, including a touchscreen and numerous applications, such as a memo pad, scheduler, calendar, world clock, contact list, and calculator. It is not known if Samsung plans to launch an e-book store and which formats its e-reader will support, yet both of these factors could have a serious impact on Samsung’s success.

	E-books have come a long way and many of the features that were previously lacking have been added to the newer devices, such as the ability to annotate text. While e-book readers may already be ideal for reading novels and other text-heavy pieces, some improvements may be needed before they will be an ideal platform for all textbooks. For instance, none of the currently available readers display in color, which may be especially important for a pathology textbook, though not at all important for a math textbook. Regardless, with more players entering the e-book arena, there appear to be some exciting developments on the horizon, so stay tuned.

Maurie Markman, MD, is Editor-in-Chief of Oncology Net Guide and Vice President of Clinical Research for University of Texas MD Anderson Cancer Center in Houston, Texas

Electronic communication technologies have radically changed our world, transforming almost every aspect of our daily lives. Most of the tasks we need to perform can be handled electronically, from paying bills and shopping to communicating with friends and family.

August 2009 | Oncology Live®

Ovarian Cancer Screening Focuses on Improving Early Detection

E-books: Will they impact education and dissemination of medical information?