	The Future of Molecular Epidemiology: New Tools, Biomarkers, and Opportunities

	BHGI Global Summit on International Breast Health

	Federation of Clinical Immunology Societies 10th Annual Meeting

www.calgb.org/Public/meetings/meetings.php

	12th World Congress on Gastrointestinal Cancer

	American Brachytherapy Society Prostate Brachytherapy School

	International Conference on Modern Cancer Management

	ASCO/AACR Methods in Clinical Cancer Research

	16th Annual Perspectives in Breast Cancer

	International Society of Gastroenterological Carcinogenesis Conference

	Joint Metastasis Research Society-AACR Conference

	15th European Society of Surgical Oncology Congress

	4th Annual Perspectives in Genitourinary Oncology

	4th American Association for Cancer Research International Conference on Molecular Diagnostics in Cancer Therapy Development

	27th National Oncology Economics Conference

http://accc-cancer.org/meetings/meetings-calendar.asp

www.breastcasymposium.org/breastcasymposium/Main

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Columns

2010 Conference and Course Calendar

	The increasing popularity of social networking Websites is one of the more interesting aspects of the rapidly evolving information technology sector, as it allows families, friends, business associates, or simply people with similar interests to easily communicate with each other, either privately or in a public forum. Although numerous articles have been written on the use of social networking sites, few studies have comprehensively examined the impact of this very public forum as a means of personal communication. Nevertheless, the available literature indicates that this medium can have both negative and positive aspects.

	Consider, for example, an assault on a 12-year-old middle- school student who law enforcement personnel suspect was targeted after a Facebook group urged students to beat up redheads.

 The father of a student in the school where the event occurred said he was concerned about how the Internet may have motivated the students involved, which was no doubt a concern shared by other parents.

	A recent story in Time magazine, which examined anonymous gossip sites on college campuses, raises further concern.

 While the article appropriately notes the legitimate desire to avoid what could be classified as censorship, the effect of the current lack of accountability and the potential devastating personal impact associated with social network pronouncements—true, false, or somewhere in between&mdash; regarding an individual’s prior sexual experiences, current sexual orientation, or the presence of a sexually transmitted disease cannot be overstated.

	Finally, in a report that unfortunately hits very close to home, researchers found that 60% of medical schools that responded to a national survey noted incidents of students posting unprofessional online content.

 Such content included profanity, discriminatory language, depiction of intoxication, and sexually suggestive material. While this report should perhaps not come as a surprise to anyone, it will hopefully serve as a “wake-up-call” regarding the need for medical (and pre- medical) educational efforts in this arena, and the need for carefully considered (but essential) disciplinary strategies when such material is uncovered. 

	Whereas social networking sites may have negative aspects, there are also some benefi ts. One report found that social networking Websites can have a potentially favorable impact on college students, especially those who suffer from low self-esteem or are generally unsatisfied with their lives.

 For instance, people who may be particularly shy or uncomfortable in certain social situations may feel more at ease in their interactions with others.

	Online social networking is unquestionably here to stay and will likely continue to grow in both popularity and influence. As a result, additional scientific studies and analysis are needed to more fully understand this medium’s impact and potential, and it is incumbent upon medical professionals to recognize that this rapidly expanding and evolving method of communication can have both detrimental and beneficial effects on the health and welfare of their patients, families, colleagues, and the general public. 

Maurie Markman, MD, is editor-in-chief of Oncology Net Guide and vice president of clinical research for the University of Texas MD Anderson Cancer Center in Houston, Texas.

	1. Gorman A. Facebook group suspected in ‘ginger’ assault. Los Angeles Times. November 22, 2009. 

	2. Yan S. Colleges fight back against anonymous gossip sites. Time. December 7, 2009. 

	3. Chretien KC, Greysen SR, Chretien JP, Kind T. Online posting of unprofessional content by medical students.JAMA. 2009;302(12):1309-1315. 

www.ncbi.nlm.nih.gov/sites/entrez/19773566

	4. Ellison NB, Steinfield C, Lampe C. The benefits of Facebook “friends:” Social capital and college students’ use of 

 social network sites. Journal of Computer-Mediated Communication. 2007;12(4):article1.

ONCNG Oncology

The increasing popularity of social networking Websites is one of the more interesting aspects of the rapidly evolving information technology sector, as it allows families, friends, business associates, or simply people with similar interests to easily communicate with each other, either privately or in a public forum. 

Benefits and Risks of Social Networking

	In the United States, more than 200,000 women receive a breast cancer diagnosis annually. Early detection offers patients the best chance for a cure, but may also lead to treatment dilemmas in some patients. Oncology Net Guide (ONG) had the opportunity to interview Richard Bender, MD, FACP, chief medical officer of Agendia, about MammaPrint, a breast cancer recurrence assay that can help oncologists determine the metastatic potential of their early-stage breast cancer patients’ tumors.

ONG: How does MammaPrint work and what is its clinical utility?

 The MammaPrint test is performed on a fresh tumor tissue sample, and measures the gene expression profile of the 70 genes that constitute the test. MammaPrint classifies tumors as either high risk or low risk for recurrence, and when used in conjunction with other risk factors, helps identify patients who will benefit from adjuvant therapy. Compared with standard risk-assessment factors, MammaPrint significantly reduces the number of patients traditionally classified as having a poor prognosis, while at the same time identifying those patients who may be at increased risk for recurrence despite their clinical pathological findings.

Which patients with breast cancer benefit from MammaPrint testing? Or is screening a more appropriate word? 

	MammaPrint is not a screening device or service; rather, it is a gene expression profile. A breast cancer patient should meet the following criteria to be eligible:

	•Invasive carcinoma (infi ltrating carcinoma)

	•Estrogen receptor positive (ER+) or estrogen receptor negative(ER-)

What are advantages to using MammaPrint versus other types of molecular screening and how do physicians choose? 

	MammaPrint is a true next-generation breast cancer recurrence assay. Developed and validated on untreated patient samples, it is equally prognostic for patients who are either ER+ or ER- and avoids therapy requirements assumed by other tests. Based on extensive clinical discussions about early-stage breast cancer treatment thresholds—who may safely forego adjuvant therapy versus who may benefit from more aggressive therapy&mdash;MammaPrint was designed to provide a binary “low-risk” or “high-risk” result, thereby ensuring every patient result is clinically relevant and useful. With MammaPrint, physicians and their patients have an FDA-cleared test which aides in therapeutic decision- making every time, compared with other assays which often provide an ambiguous “intermediate” result. MammaPrint’s added value is supported by these differentiators, which competing assays do not provide.

The FDA has given four clearances to MammaPrint. What uses has the FDA cleared?

	In February 2007, the FDA cleared MammaPrint as a prognostic tool for patients less than 61 years with stage 1 or stage 2 breast cancer, invasive carcinoma (infiltrating carcinoma), tumor size <5.0 cm, negative lymph nodes, and ER+ or ER- tumors. In June 2007, the FDA cleared the MammaPrint fresh tissue transport methodology with RNARetain®, allowing for room- temperature shipping. In July 2008, MammaPrint was cleared to be run on a new high-density microarray, and in December 2009, FDA clearance was expanded for use in women of all ages.

How does using formalin-fixed, paraffin-embedded tissue (like OncotypeDX) affect results compared with using fresh or frozen tissue samples, like MammaPrint?

	The benefit of working with fresh tissue is that mRNA integrity is preserved. Using formalin-fixed, paraffin-embedded tissues, on the other hand, damages mRNA, leaving truncated pieces. Since genomic tests such as these rely on measuring mRNA expression levels, maintaining mRNA integrity is vital. The National Institutes of Health (NIH) Biorepository, moreover, recommends fresh tissue sampling. NIH has recently 

 the landmark I-SPY 2 trial in collaboration with the FDA, the National Cancer Institute (NCI), and a host of leading pharmaceutical and biotechnology companies. The use of MammaPrint is one of the key pivots for the study.

Risk assessments are often performed using online questionnaires, such as Adjuvant! Online and the NCI’s Breast Cancer Risk Assessment Tool based on the Gail Model. Are these tests useful and do you have anyconcerns about them?

	While such assessments are generally useful, attention should be paid to the fact that one criterion is often more heavily weighted at the expense of another. It is, therefore, crucial to understand how these tools were developed and use them correctly to help inform treatment decisions. For instance, MammaPrint is FDA-cleared to be used in conjunction with other clinical pathological criteria.

Is insurance coverage a problem with MammaPrint? 

	In December 2009, MammaPrint obtained Medicare coverage through Palmetto in California and payors reimbursing MammaPrint cover some 70 million lives in the United States. Currently, MammaPrint falls under a generic CPT code, 84999. A number of private payors reimburse for MammaPrint and Agendia is in discussions to have MammaPrint included in their policies.

What is TargetPrint® and how does it work with MammaPrint? 

	TargetPrint is a microarray-based gene expression test that offers a quantitative assessment of the level of ER, progesterone receptor (PR), and HER2/neu overexpression in a patient’s breast cancer. It is offered in conjunction with MammaPrint to provide physicians with a more comprehensive information set to help guide treatment decisions. As compared with immunohistochemistry (IHC), TargetPrint delivers an added benefi t to the diagnostic process. While IHC provides a semi-quantitative positive or negative result, the gene expression result provided by TargetPrint allows physicians to integrate the absolute level of ER, PR, and HER2 gene expression for these three biomarkers into treatment planning. The tests are performed on quality-controlled DNA microarrays in Agendia’s state-of-the-art CLIA (Clinical Laboratory Improvement Act) and CAP (College of American Pathologists) registered and compliant genomics laboratories in Huntington Beach, California, and Amsterdam, The Netherlands.

	Yes, MammaPrint is used worldwide, although our commercial focus is on the US market and principal European markets.

Any additional plans for MammaPrint that you can 

	On March 17, Agendia announced that MammaPrint is to play a pivotal role in the I-SPY 2 trial (http://ispy2.org). The trial, which I briefly mentioned earlier, is supported by the NIH, NCI, FDA, and a host of leading pharmaceutical and biotechnology companies. Specifically, information from Agendia’s genome expression profiling will provide “snapshots” of tumor biopsies before and after administration of the neoadjuvant therapies under investigation. Combined with data from the other trial participants, this promises to accelerate trials, reduce patient enrollment numbers, and generate huge savings for commercial, research, and governmental institutions. In short, I-SPY 2 aims to help change the way clinical trials are conducted and biologics and pharmaceuticals are developed.

	Additionally, Agendia recently launched BluePrint, which is a new microarray-based 80-gene expression profi le which classifies a woman’s breast cancer into the Basal-type, Luminal-type, or ERBB2- type (HER2+) molecular subtypes. Agendia also launched TargetPrint Research Gene Panel, a gene expression panel of 56 genes identified as potential targets for therapeutic response to a variety of treatment for breast cancer. Both of these new signatures hold promise for improved understanding about a patient’s unique tumor biology, and perhaps the key to a greater level of personalized care.

Looking for more information on MammaPrint? Consider these 4 articles: 

Gene expression profiling: Decoding breast cancer 

	AUTHORS: de Snoo F, Bender R, Glas A, Rutgers E.

	CITATION INFORMATION: Surg Oncol. 2009;18(4):366-378.

www.ncbi.nlm.nih.gov/sites/entrez/19879448

Validation of 70-gene prognosis signature in node-negative breast cancer 

	AUTHORS: Bueno-de-Mesquita JM, Linn SC, Keijzer R, et al.

	CITATION INFORMATION: Breast Cancer Res Treat. 2009;117(3):483-495.

www.ncbi.nlm.nih.gov/sites/entrez/18819002

Metastatic potential of T1 breast cancer can be predicted by the 70-gene MammaPrint signature 

	AUTHORS: Mook S, Knauer M, Bueno-de-Mesquita JM, et al.

	CITATION INFORMATION: Ann Surg Oncol. 2010;17(5):1406-1413.

www.ncbi.nlm.nih.gov/sites/entrez/20094918

The predictive value of the 70-gene signature for adjuvant chemotherapy in early breast cancer 

	AUTHORS: Knauer M, Mook S, Rutgers EJ, et al.

	CITATION INFORMATION: Breast Cancer Res Treat. 2010;120(3):655-661.

www.ncbi.nlm.nih.gov/sites/entrez/20204499

Tech Sectors


In the United States, more than 200,000 women receive a breast cancer diagnosis annually. Early detection offers patients the best chance for a cure, but may also lead to treatment dilemmas in some patients.

Examining MammaPrintÂ®: An Interview with Richard Bender, MD

	Bone Therapy in Breast Cancer: Why, When, and What’s Next? (

	Talking with Your Patients about Clinical Trials (

	Cancer Fatigue and Contributing Factors: Recognition and Treatment (

	Health Care Reform: Resetting the Clock (

	Optimizing Care of the Elderly and Underserved (

	Predictors of Response to Preoperative Therapy: Where Are We? (

	Addressing the Cost of Cancer Care with Patients: Practice-based Strategies for Communicating the “New Bad News”

	Physician Burnout: How to Survive and Stay Happy in Oncology (

	Developing Drugs in Special Populations: Organ Dysfunction Studies (

	Advancing Pain and Palliative Care Globally for Patients with Cancer (

2010 Asco Annual Meeting

	The boisterous crowing from camp Apple can deafen consumers to iPhone alternatives; however, the Google-backed 

 operating system has been gaining traction. The new crown jewel in the emerging Android empire is the 

. Due to marked similarities in appearance and functionality, the Desire is considered a “cousin” to Google’s Nexus One. The Desire measures 119 mm x 60 mm x 11.9 mm and weighs 135 g (with battery). It has a 3.7- inch AMOLED multi-touch screen, 3G Internet, an optical trackpad, 576 MB of RAM, 512 MB ROM, a 5-megapixel camera, and is Bluetooth enabled. The Desire runs on a 1 GHz Snapdragon processor and its HTC Sense interface allows users to personalize their phone experience using various widgets. Thousands of apps are available through the handset itself or Android Market, Android’s “through the looking glass” version of iTunes App Store. If the constant buzz surrounding cell phones and brain cancer has you worried, rest assured, the Desire’s radiation emission, as measured by its specifi c absorption rate (SAR), is 1.12 W/kg, which is below the FCC’s maximum allowance of 1.6 W/kg. If you decide to join Team Android, keep abreast of updates; phone models quickly become obsolete in emerging technology markets.

 that will allow you to enhance, electronically file, or e-mail patient imaging? Canon’s CanoScan 8800F Flatbed Scanner creates scans in seconds with a resolution of up to 4800 x 9600 color dpi. Its 48-bit color depth produces over 281 trillion possible colors and included software can enhance resolution to 19,200 color dpi. The 8800F’s frame measures 10.7 inches (width) x 18.9 inches (depth) x 4.0 inches (height), and the unit weighs 9.2 pounds. Seven large function buttons automate the scanning process, making it easy to scan, copy, and create e-mails and PDFs. You can batch-scan up to twelve 35-mm frames or up to 4 slides. Built- in retouching technology improves image quality by removing imperfections such as dust and scratches.

	The 8800F is compatible with multiple Windows and Mac operating systems. High-luminance white LED lamps eliminate the always-frustrating machine warm-up period. This convenience also lowers energy consumption, a Canon goal under its new Generation 

 initiative. Also on the “Go Green” front, the 8800F is Energy Star qualified, which means it meets energy efficiency guidelines set by the US Environmental Protection Agency and the US Department of Energy. Canon offers warranties of varying length and technical support for the 8800F via e-mail and phone.

	Need a clear, hands-free mobile connection to your office when you are on the go? You may want to try the 

 Icon wireless Bluetooth headset. The Icon’s NoiseAssassin military-grade technology eliminates ambient sound so your voice is clear regardless of your surroundings. The device’s standard specs are 45 mm x 18.25 mm x 24 mm and 8.2 g, and syncing it with your phone should be quick and easy. The Icon package includes an assortment of rubber rings for various ear sizes and an optional hook for additional stabilization. The earpiece should get up to 4.5 hours of talk time and up to 10 days of standby time. Enviros will appreciate the Icon’s 100% recyclable packaging. Consumers can choose between six named designs varying in color and texture: the Catch, the Rogue, the Hero, the Thinker, the Bombshell, and the Ace. These monikers also correspond to the different voices with which the Icon communicates the battery’s charge level or incoming call numbers. Changing the voice entails using an app, as the Icon is the first Bluetooth earpiece to offer the popular downloadable software add-ons. Uploading the few available apps involves a somewhat tedious process requiring hookup with your Mac or PC; however, you will appreciate the personalization.

Gadget Watch

	In a presentation at the Third Annual Interdisciplinary Prostate Cancer Congress (IPCC), Howard M. Sandler, MD, MS, a Ronald H. Bloom Family Chair in Cancer Therapeutics and professor and chair of the Department of Radiation Oncology at Cedars Sinai Medical Center in Los Angeles, California, spoke on the latest technologies in radiation oncology. The IPCC was hosted by ArcMesa Educators in New York, New York, on March 27, for medical oncologists, urologists, radiation oncologists, and others who treat patients with prostate cancer.

	Sandler noted that there have been many technological advances in radiation oncology centers in the use of intensity-modulated radiation therapy (IMRT). He compared IMRT to the older standard of 3D conformal radiotherapy (3D-CRT) to treat prostate cancer. “[3D-CRT] is not bad, but things have gotten better with IMRT,” he said. Sandler noted that the rectum is the primary organ at risk for radiation-related toxicity and that IMRT has lessened radiation exposure compared with 3D-CRT. According to Sandler, 3D-CRT delivers high doses to and around the prostate. “With IMRT, we get much more rounded, conformal dose distribution, where a high dose is delivered to the prostate and a relatively low dose to surrounding structures.” He singled out the rectal-prostate interphase as an area where IMRT affords a steep drop in the gradient of dose. “The difference in dose to the rectum between IMRT and 3D conformal type of distribution is clinically important,” said Sandler.

	IMRT is more effective, Sandler said, because “lead leaves move in and out under computer control and create very structured radiation dose fields...instead of creating a beam of radiation, you break the beam up into small beamlets of about 1 cm x 1 cm.” He told the audience that they could get a sense of how intensity modulation directed at the prostate works by envisioning 200 penlights, each aimed at the prostate and each individually adjustable in intensity. The intensity modulation optimization program with IMRT, he explained, is smart enough to ensure that a beam coming through the prostate and exiting the rectum does not deliver too much radiation to the rectum. A dose-volume histogram (DVH) depicts the dose of radiation delivered to different organs. Sandler polled colleagues at several well-known radiation facilities and learned that everyone uses different spots on the DVH to optimize radiation delivery with IMRT.

	In Sandler’s poll, he asked his colleagues how they would treat someone with a diagnosis of intermediate risk prostate cancer and found that most institutions use overall doses ranging from 75 Gy to 80 Gy. “Radiation kills cells,” said Sandler. “Tumor and early-responding tissue, like mucosal, have an alpha- beta ratio of ~1 to 10, while late-reacting tissues, or prostate cancer, may have a different alpha-beta ratio than other cancers, at ~1 to 3.”

	Investigators have been looking at whether giving higher daily doses of radiation in fewer fractions is as effective as standard radiation. This is known as hypofractionation, and Sandler said it should be equal to or better than standard radiation delivered with a lower dose but a greater number of fractions. “A hypofractionated regimen delivers a lower dose of radiation overall, and some studies suggest it is associated with fewer adverse effects,” he said.

) 0415 is a phase III randomized study comparing hypofractionated 3D-CRT/ IMRT with conventionally fractionated 3D-CRT/IMRT. The trial has accrued 800 patients with stage T1c to 2a prostate cancer who have a Gleason score <7 and a PSA level <10 ng/mL. The endpoint of the study is 5-year biochemical failure. Sandler said preliminary data suggest a 70 Gy/28 fraction regimen is just as effective as a 73.8 Gy/41 fraction regimen. The study recently closed, and Sandler said he expects additional data to become available in about 3 years.

Fiducial markers to track prostate movement 

	One of the key concerns when using IMRT that Sandler honed in on is the potential of the prostate to move with respect to the pelvis. “A CT [computed tomography] scan with 3 metal fiducial markers showing where the prostate is, taken just before the patient is about to be treated, may not accurately indicate the location of the prostate,” he said. Various factors can cause the prostate to shift, such as a gas bubble or even breathing. For example, breathing moves the prostate about two-tenths of a millimeter, which may not seem like much but is important when administering radiation. Daily prostate localization, said Sandler, is critical when using IMRT or other highly conformal strategies.

	Sandler said an AC wireless magnetic tracking system such as the Calypso 4D can help improve the accuracy of radiation delivery to the prostate. Calypso is a continuous tumor-localization system that uses radiofrequency markers, or transponders, implanted in the prostate to assess the organ’s position to the submillimeter. A console delivers an electromagnetic pulse to the transponders, which respond by emitting radiofrequency waves. These are received at the console and used to show where the prostate is in real time—left, right, in and out, and up and down. “In a study we did at the University of Michigan,” said Sandler, “over a course of 7-minute treatment sessions over 10 days for a patient, we found that the prostate might move several millimeters during treatment.” He said the patient’s prostate sometimes moved out of the beam entirely, which could have resulted in under-dosing. “If you have this real-time information, you can quickly correct for intra-treatment prostate motion,” Sandler said. Implanted fiducials have become the standard of care, and Sandler said he asks his urologist to put them in all his patients before treatment. “It is safe and allows us to reduce the margins because we know where the prostate is all the time. It is also reimbursable as part of image-guided radiation therapy [IGRT].”

	On the question of whether to treat pelvic lymph nodes, Sandler said some evidence suggests it might be useful. The landmark RTOG 9413 study showed some benefit to treating pelvic lymph nodes with radiation. Sandler compared treating pelvic lymph nodes using 3D-CRT to IMRT, saying, “In the 3D-CRT era, we would treat a block in the pelvic area, including a loop of bowel that would be treated unnecessarily. With pelvic-nodal IMRT, we draw where the lymph nodes are, add a margin for uncertainty, and end up with significantly less bowel exposure.”

	Several other radiotherapy technologies exist or are in various stages of development. Radiation damage to the prostate can have serious adverse effects for the patient, including incontinence and impotence, which have a tremendous negative impact on quality of life. Researchers have devoted considerable resources to identifying strategies to treat prostate tumors in a way that kills the cancer cells but spares the healthy tissue—and, hopefully, prevents some of radiation’s worst effects.

 RapidArc radiotherapy is another IMRT technique. “This is a fast way to do IMRT, within 2 to 5 minutes instead of 15 minutes, making radiation therapy departments more efficient,” Sandler said. With RapidArc, treatment is delivered in an arc-like fashion, and the leaves aimed at the prostate move as the arc movies. RapidArc delivers a focused dose to the prostate, with scattered low doses of radiation landing outside the area.

 TomoTherapy was first used to treat patients in 2002 at the University of Wisconsin. It combines integrated CT imaging with IMRT. A standard 6 MV linear accelerator is mounted on a ring gantry and rotates around the patient as he moves through the machine. “I consider TomoTherapy to be just another way of doing IMRT,” said Sandler. “It is not superior to any of the other techniques [and] has roughly the same RDV histogram as other methods.” TomoTherapy says its “beam on” times are comparable to normal radiation therapy, averaging 3 to 5 minutes for a common prostate treatment. It is currently being used in several countries to treat multiple solid tumor types, including lung cancer, malignancies of the head and neck, breast tumors, and prostate cancer.

 CyberKnife, another prostate cancer treatment whose use is increasing, is a stereotactic radiosurgery system that delivers high-energy IGRT. It consists of a 6 MV linear accelerator mounted on an industrial robot arm, which is computer controlled. “It has imaging devices and a panel that can take standard kilovoltage radiographs for monitoring where the tumor is while you are using it to treat a patient,” said Sandler. Unlike a Gamma Knife, the CyberKnife is not frame-based and can be used to treat tumors virtually anywhere in the body. Sandler discussed a 2007

 by Pawlicki and colleagues that showed that CyberKnife offered near real-time target tracking (q30-90 sec) and took approximately 40 minutes for prostate treatment. “CyberKnife allows a total prostate cancer treatment in 7.25 Gy/fractions for a total dose of 36.25 Gy, which may equal 8 weeks of treatment,” Sandler said. He added that it is unclear whether 1 week is equal in efficacy to 8 weeks and various studies are underway to determine this. “I am concerned about toxicity or under-dosing... there is very little data on this,” he said. Last year, the American Society for Therapeutic Radiology and Oncology (ASTRO) published a position paper describing this type of approach as investigational. As a result, Sandler said many insurers do not cover CyberKnife. “It would not surprise me...if CMS [the Centers for Medicare & Medicaid Services] stops covering this, as well,” he added.

 Sandler noted there are several manufacturers that make state-of-the-art commercial accelerators, including Siemens, Varian Triology, and Elekta Synergy. These typically have arms on the side that provide opportunities for imaging, he said, because locating the exact position of the tumor in real time is becoming increasingly important to radiologists. Other systems are the BrainLAB by ExacTrac and the Medical Intelligence Hexapod Couch. “Patients sit on these tables that go up and down and in and out. There has been an effort to try to make these tables more sophisticated and allow the tables to rotate to account for differences in patient positioning,” he explained.

 Stereotactic hypofractionated accurate radiotherapy of the prostate (SHARP) is slightly different than IMRT and operates similarly to CyberKnife. SHARP delivers a highly focused beam of radiation that Sandler said is “extremely tight on the target.” In 2007, Madsen and colleagues reported 

 from a phase I/II trial that used SHARP to treat 40 men with localized prostate cancer. Investigators administered 33.5 Gy in 5 fractions, which the authors said was the biological equivalent to 78 Gy in 2 Gy fractions (alpha-beta ratio of 1.5 Gy). The median follow-up was 41 months. Grade 1-2 acute toxicity was 48.5% genitourinary (GU) and 39% gastrointestinal (GI). The study reported one case of grade 3 GU toxicity but no late toxicity of grade 3 or higher was reported. Of the 26 patients who were potent prior to therapy, 6 (23%) developed impotence. The median time to PSA nadir was 18 months, with most nadirs <1.0 ng/mL. The authors concluded that dose escalation should be possible. Radiation oncologists at Virginia Mason 

 SHARP and say it reduces treatment time from the standard 8 weeks to 5 days. 

	In discussing particle therapy, Sandler explained the differences between conventional photon (X-ray) therapy and proton therapy. A cyclotron whips the protons around very quickly using powerful magnets, then uses additional magnets to direct a beam of protons out of the cyclotron. “When you administer proton therapy...the beam [of protons] comes in with a low dose, remains at a low dose, and then near the end of the range of the proton, it deposits most of its energy,” he said. This burst of energy that the protons release at the end of their journey—generally at the tumor site&mdash;is known as the Bragg peak. The total dosage of radiation is referred to as the spread-out Bragg peak (SOBP). Controlling the speed of the proton allows the precise depth at which it expels its energy to be manipulated. This potentially helps deliver a higher dose to targets deeper inside the patient and spares more healthy tissue. Tissues behind the tumor or deeper than the tumor receive little radiation exposure, and the dosage to tissue in front of the tumor or not as deep as the tumor is determined by the SOBP.

	In contrast, photon therapy directs electromagnetic waves (or X-rays) through the skin, which deliver a continuous dose until they exit. Unlike protons, X-rays lack charge and mass. They always deliver substantial doses of radiation anterior and posterior to the tumor. The biological effects of proton therapy, Sandler said, do not differ fundamentally from those associated with photon therapy. “When we use X-ray (or photon) therapy, we activate electrons that hit DNA or turn water into [free] radicals that damage DNA. Proton therapy activates those same electrons, and it is the electrons that do the damage.” Proton therapy does not directly interfere with DNA. Sandler said because proton therapy conducts more of the dose to the tumor, it might afford increased tumor control and reduce treatment-related toxicities, such as tissue damage and second cancers, which he noted is especially important for pediatric patients.

	“Is there scientific evidence for doing proton therapy?” Sandler asked hypothetically. A few articles were published in the Journal of Clinical Oncology in 2007, he said, that found little evidence to support the use of proton therapy. Brada and associates reviewed data from 36 published

 on proton therapy, only 2 of which were phase III. The studies involved patients with chordomas, chondrosarcomas, ocular tumors, prostate cancer, and head and neck cancer. The authors found that patients with chondrosarcomas had a 5-year local PFS of 95%, which was no better than PFS associated with conventional therapy. Compared with photon radiotherapy, none of the studies using proton therapy in localized prostate cancer demonstrated improved tumor control or increased survival, nor was there clear evidence that proton therapy resulted in less toxicity. The authors concluded, “Proton and other particle therapies need to be explored as potentially more effective and less toxic radiotherapy techniques.”

 at Massachusetts General Hospital in Boston that compared IMRT to proton therapy, Trofimov and associates found that proton therapy might produce less low-dose exposure outside the tumor area, possibly reducing the risk of second cancers. “In the high-dose area, I don’t see much of an advantage, if any,” Sandler said. In looking at medulloblastoma, proton therapy was found to give “exquisite protection” to a child’s organs. “For pediatric patients, proton therapy may be the treatment of choice. For a 70-year-old man who has a small risk of a radiation-induced cancer, it is hard to justify proton therapy,” he said. Sandler concluded that the evidence for proton therapy in prostate cancer is not well established and more research is needed to determine which patients are likely to benefit from proton technology.

	“Assuming that you can give higher doses with proton therapy and that it is more effective, it is still not cost-effective,” he said. A 2007 

by Konski and colleagues compared a dose of 91.8 Gy for proton therapy versus 81 Gy for IMRT and found proton therapy to be more expensive. According to the authors, proton therapy cost $63,500 per quality- adjusted life year (QALY) for a 70-year-old man and $55,700 per QALY for a 60-year-old man, whereas the commonly accepted standard for cost-effectiveness in radiotherapy for prostate cancer is $50,000 per QALY.

	In addition to being the most expensive radiation treatment to administer to prostate cancer patients, proton therapy is also the most expensive when it comes to building and running a proton treatment facility, though Sandler said some centers might consider it worthwhile from a business perspective. “Any big radiation facility is either buying protons or they’re talking about buying protons,” he noted. In the United States, active proton facilities exist at Loma Linda, Indiana University, University of Texas MD Anderson, University of Florida at Jacksonville, Massachusetts General Hospital, Oklahoma City, and the University of Pennsylvania. Many others are planned, including one at Hampton University in Virginia and one at the Cancer Alliance in Seattle. “Once you have an expensive cyclotron, you can steer the beam into multiple rooms,” Sandler said, “and treat several patients at once.” These rooms are called gantry rooms, and each room is equipped with a system to modulate the energy of the proton beam according to the patient’s needs. Given the cost-benefit ratio for proton therapy, said Sandler, establishing regional centers makes better sense for very expensive technologies like these.

	Cancer centers that offer proton therapy frequently advertise the service on the radio, Sandler said, touting its benefits as a prostate cancer treatment and convincing men with the disease to seek proton therapy. He pointed to a press release from the 

 of the Loma Linda University Medical Center’s proton facility that said patients with prostate cancer are more likely than patients with any other cancer to receive proton therapy and “a vast majority” of the men self-refer themselves.

	As a counterstrategy to MD Anderson’s successful advertising of its proton facility, the University of Texas Southwestern is looking into carbon ion therapy. Sandler called carbon ion therapy “the next escalation in the technology war.” Because a carbon nucleus weighs 12 times as much as a proton, a much larger cyclotron is needed to accelerate it. “It has interesting biological differences,” Sandler said, and he noted that there are currently no carbon ion facilities in the United States.

MEDCAC reviews radiation therapy for localized 

	Given the cost of proton therapy, when Sandler saw that the Medical Evidence Development & Coverage Advisory Committee (MEDCAC) had scheduled a meeting on April 21 on “radiation therapy for localized prostate cancer,” he assumed that CMS might be looking for a way to deny coverage for the therapy. He was surprised to see instead that the topic on the agenda was whether MEDCAC was confident there was adequate evidence to determine whether radiation therapy to treat localized prostate cancer improves mortality and functional outcomes, with manageable adverse events. CMS also said it wanted to compare radiation therapy to a strategy of watchful waiting, which Sandler said “shows that CMS does not even understand the field very well, because ‘watchful waiting’ is not the correct term of art for this.” The agenda also singled out stereotactic body radiotherapy and CyberKnife for extra scrutiny.

	CMS created MEDCAC several years ago to advise the agency on what Medicare should or should not cover based on the adequacy of scientific evidence. Sandler said MEDCAC comprises approximately 100 members and is an important committee whose recommendations often affect radiation oncologists. “I think with healthcare reform it is going to become even more important,” he added. Sandler identified MEDCAC as the group that suggested CMS no longer cover CT colonoscopy, a recommendation CMS adopted. He expressed concern and said he and others in the field of radiation oncology would be speaking at the meeting. To learn more about MEDCAC and watch for updates on this important meeting, visit 

	The full IPCC conference included discussions on a range of issues related to prostate cancer, including prevention, treatment, diagnosis and immunotherapy. Watch for coverage of these sessions in 

 In addition, videos from the conference will be posted soon at the ArcMesa Educators 

Cover Story

In a presentation at the Third Annual Interdisciplinary Prostate Cancer Congress (IPCC), Howard M. Sandler, MD, MS, a Ronald H. Bloom Family Chair in Cancer Therapeutics and professor and chair of the Department of Radiation Oncology at Cedars Sinai Medical Center in Los Angeles, 

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