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.

According to the Centers for Disease Control and Prevention, colorectal cancer is the second leading cancer killer in the United States, affecting both men and women. In 2005, the latest year for which 

 is available, 141,405 people received a colorectal cancer diagnosis and more than 53,000 died from the disease. Until the mid-90s, the only approved agent for treating this cancer was 5-fluorouracil (5-FU), and although other agents are now readily available, 5-FU is commonly the backbone of combination chemotherapy.

	While calculating body surface area (BSA) is the standard of care for determining a patient’s infusional 5-FU dose, BSA measurements often fail to identify the optimal dose because they do not consider the countless factors beyond height and weight that affect 5-FU metabolism and efficacy. Now oncologists who administer a 5-FU-based treatment regimen can use a simple blood test, distributed by Myriad Genetic Laboratories, to individualize this therapy for their colorectal cancer patients, ensuring an optimal dose is administered in this population. The blood test, called OnDose

, was launched in April 2009 and could be used in about 175,000 patients in the United States.

	The side effects of 5-FU treatment can be severe and may include diarrhea, mucositis, dermatitis, cardiac toxicity, and myelosuppression. In rare cases, these toxicities can result in death, especially in the setting of a dihydropyrimidine dehydrogenase (DPD) deficiency, an autosomal recessive metabolic disorder that results in absent or significantly decreased activity of DPD, an enzyme that metabolizes uracil and thymine. Recent 

 suggest that 8% of the general population may have at least a partial DPD deficiency; thus, a rather substantial number of patients with colorectal cancer could be at risk of adverse events when only BSA calculations are used to determine their 5-FU dose.

	Blood levels of 5-FU have been found to exhibit a 10- to 50-fold variability between individuals despite equal 

. This is because many factors affect 5-FU metabolism and efficacy, including age, race, sex, genotype, drug-to-drug interactions, and disease state, yet current standards of care focus only on height and weight through BSA calculations to determine dose. In a 2008 article by Gamelin and colleagues, published in the 

, the authors noted that up to 85% of patients are not dosed optimally using the conventional 

, which places these patients at increased risk of toxicities, premature treatment termination, disease progression, lack of therapeutic response, and higher treatment costs. OnDose allows oncologists to rapidly assess their patients’ 5-FU blood levels and exposure to 5-FU during infusion, helping to dose them more optimally.

	OnDose requires a small peripheral venous blood sample to be taken during steady state, between two hours after the start of a continuous infusion to the end of the infusion, provided the infusion pump is still running. The sample is then centrifuged to extract a 1-mL plasma sample from the collected blood. The plasma is frozen overnight (minimum temperature, -15°C) and then shipped to Myriad labs in a supplied cold shipping container the next business day for analysis. The sample is assessed using a competitive homogenous two-reagent nanoparticle agglutination immunoassay, and the results are returned to the clinician within 7 days. A quantitative target range is outlined in the report, and the clinician can then adjust the patient’s next dose, if needed, to achieve a 5-FU blood level in this range. The test is conducted each cycle of treatment until the patient achieves a 5-FU level in the target range and maintains a level in this range for three treatment cycles, after which the test can be performed every three cycles.

	The OnDose list price is $300 per test, but the test has been added to the majority of contracts with public and private insurers, which now provide coverage for the test. There are also options for uninsured patients and those whose insurance may not cover the test. For the latter group, Myriad offers the OnDose Patient Protection Program, which limits the out-of-pocket costs of qualified patients to 20% of Myriad’s billed charges after the patient’s deductible has been met. The OnDose Patient Protection Program is not available to patients covered under Medicare, Medicaid, or other government programs, or those residing in states where such programs are prohibited, including Florida, Massachusetts, Texas, Minnesota, and Rhode Island. Some patients who are uninsured and meet established clinical and financial criteria can receive the test free through the Myriad Financial Assistance Program (MFAP). Eligibility requirements for the MFAP program can be found at 

PK-guided therapy: Data and implications 

 published a phase III, multicenter study that compared BSA-based dosing of infusional 5-FU plus folinic acid (leucovorin) with 

. The study randomized 208 patients with measurable metastatic colorectal cancer to an arm in which the 5-FU dose was calculated based on BSA (n = 104) and to one in which the 5-FU dose was individually determined using pharmacokinetically (PK)-guided adjustments (n = 104). The initial regimen was 1,500 mg/m

 of folinic acid administered via infusion once weekly during a continuous 8-hour period. The 5-FU doses were adjusted weekly in the PK-adjusted arm based on a single-point measurement of 5-FU plasma concentrations at steady state until the therapeutic range was reached.

	An intent-to-treat analysis of the 208 patients showed the objective response rate was 18.3% in the BSA arm and 33.7% in the PK-guided arm (P = .004). The PK-guided arm also had a greater median overall survival than the BSA arm (22 months versus 16 months, respectively; P = .08) and fewer toxic adverse events (P = .003). Based on these findings, the authors concluded that there is value in PK-guided therapy of patients with metastatic colorectal cancer receiving 5-FU therapy.

	In a Myriad press release, Edward Chu, MD, deputy director of the Yale Cancer Center in New Haven, Connecticut, noted “the introduction of OnDose is a new and vitally important advance in cancer care,” stating that “for the first time, a fast and accurate method of measuring and monitoring 5-FU blood levels will now be accessible to the practicing oncologist.” For more OnDose information, visit Myriad at 

Lisa LaMotta is a freelance writer from New Jersey. She has written for Forbes, Fast Company, PRWeek, and New York Press.

Articles

According to the Centers for Disease Control and Prevention, colorectal cancer is the second leading cancer killer in the United States, affecting both men and women.

5-FU Dose Optimization: Another Step Towards Personalizing Cancer Care

	“In most cancer centers, and in good community practices, we do a pretty good job at the time of diagnosis informing a patient and their family what the diagnosis is, and what they’ll need to do to get through treatment,” Ganz says. “But patients often have no idea what to expect once they’ve finished their cancer treatment, and neither do the primary care providers on their team.”

, and the National Coalition for Cancer Survivorship (

, a pilot program in California, Colorado, Maine, Nevada, and New Hampshire to promote physician and patient understanding of the post-treatment effects of cancer.

	Michael Belman, MD, MPH, medical director for Anthem Blue Cross, a WellPoint company, says that one of the biggest issues in healthcare delivery is the fragmentation and lack of coordination among primary care physicians and specialists. That fragmentation, he adds, is particularly noticeable in the oncology world. “Oncology is such a highly complex specialty, and primary care physicians feel in some cases a certain amount of insecurity dealing with these patients. In the absence of communication, it’s very difficult for primary care physicians to pick up and manage these patients with confidence.”

	The challenge, says Ganz, is that there are approximately 12 million cancer survivors, and each year that number grows by about one million new diagnoses. “We need to find some way to make this [coordination of care] easier for docs to do.” That “way,” at least initially, may be the Survivorship Care Plan Builder, a kit that Journey Forward is distributing to healthcare providers and patients. These kits, which will initially focus on breast and colon cancer survivors, will explain the importance of follow-up care plans, offer tools for providers to generate these plans, and provide interactive tools for patients to participate in the process. The kits are also available for download on the Journey Forward Website, with the 

r. The Survivorship Care Plan Builder has several useful features, including utilities that make the preparation of the patient’s treatment summary and follow-up care plan quick and easy, such as a regimen library, body mass index calculator, and checklists that significantly reduce data entry. Oncologists also have the ability to customize patient care plans with their practice’s logo and are enabled to expand individual care plans with valuable resources, such as a directory of support services, a list of symptoms that patients and physicians should watch for, and information on late- and long-term effects of chemotherapy treatment. Further, since the Survivorship Care Plans produced by the tool reside on the individual practice’s computer, they can be modified, e-mailed, or printed, and are completely private. According to Jennifer Hausman, MPH, clinical research manager for Anthem Blue Cross, the intent of these plans is to keep everyone on the same page. She notes that although the plan is put together by the oncologist, “they then give a copy of the completed care plan to the primary care physician or physicians involved as well as the patient.”

	Susan Silver, senior director of communications and programs for NCCS, says the transition from cancer patient to cancer survivor is universally challenging. While patients are in treatment, they know who is watching over them and what they’re supposed to do from week to week. When treatment ends, however, they’re left wondering what’s next? “Cancer is a serious illness. And even when you’ve completed treatment, and in some cases have been told there is no evidence of disease, it’s very common and understandable for people to be concerned that they have special healthcare needs.”

	Jason Zimmerman, a cancer survivor and advocate, is one of those people. Zimmerman was diagnosed at 6 months of age with neuroblastoma of the left neck. The tumor was surgically removed, he was treated with radiation, and had checkups every three to six months thereafter. At age 15, however, he was diagnosed with thyroid cancer. He received a thyroidectomy and more radiation, but six years later, just after graduating from college, a recurrence of the thyroid cancer was detected. Following more radiation, he was given a clean bill of health, and has been cancer-free for the last 11 years. But, it was a long, hard road.

	“When you’re 15, you’re just trying to find yourself, so I was dealing with that, and then dealing with [the thyroid cancer],” Zimmerman recalls. “And then going back to school ... the way I felt was that people were looking at me differently and treating me differently. I just wanted to be a regular kid in high school like everybody else. And there was no information that you should look for a secondary cancer down the line, or look for any other physical issues that could be the result of treatment or surgery.”

	Journey Forward’s survivorship care plan, Zimmerman says, is important because it keeps records and treatment summaries together. There’s a plan for checkups, and an idea of what patients should look for. “It gives you the idea that you’re being proactive in keeping an eye on your body, because the thoughts of recurrence are always there. Sometimes they’re in the back of my mind, but they’re ever-present,” he said.

	WellPoint has mailed the kit to oncologists and distributed a patient version to breast and colorectal cancer survivors. Postcards are also being sent to primary care doctors serving WellPoint to keep them informed. “This is free, anybody can use it,” says Ganz. “And the care plan is flexible and can be tailored by the doctors as they choose.”

Ed Rabinowitz is a veteran healthcare journalist based in Bangor, PA.

"In most cancer centers, and in good community practices, we do a pretty good job at the time of diagnosis informing a patient and their family what the diagnosis is, and what they'll need to do to get through treatment," Ganz says. "But patients often have no idea what to expect once they've finished their cancer treatment, and neither do the primary care providers on their t

Collaborative Effort to Address the Needs of Cancer Survivors  

	Eight years ago, Walter Baile, MD, and his colleagues at the University of Texas MD Anderson Cancer Center developed a CD-ROM called the “Practical Guide to Communication Skills in Cancer Care.” It was the first step in teaching healthcare professionals how to effectively communicate with cancer patients and their families.

	“Communication is so important,” says Baile, a professor of behavioral science at MD Anderson. “Because if we’re not informing our patients correctly, if we’re not understanding their concerns, then we’re only doing half a job. You can cure the disease but not necessarily heal the patient.”

	More recently, Baile and his colleagues have taken the videos from the CD-ROM, built them into educational modules, and posted them to the Internet, making them easily accessible to all clinicians. The resulting online education tool, called I*CARE, or Interpersonal Communication and Relationship Enhancement, has been up and running since January 2009. In the first six months, the 

, which includes video lectures, patient scenarios, articles, and other resources designed to improve physician-patient communication.

	At MD Anderson, Baile and his colleagues are in contact with oncologists on a daily basis, and they conducted several surveys to assess what oncologists felt were their most difficult communication challenges. Several evidence-based patient scenario videos resulted, and the content on these videos is derived from the shared experiences of actual cancer patients and their families. The scripts that were developed represent actual communication encounters that occur between cancer patients and their clinicians.

	One of the leading challenges that cancer clinicians face is identifying and responding to strong emotions in patients. Those emotions are, at least in part, a result of what Baile calls cancer’s social stigma. He points to a survey conducted by the 

where 38% of respondents indicated that cancer is the worst thing that could ever happen to someone.

	“When people think about cancer, they think about dying, and they think about suffering,” he explains. “The anxiety and the fear that are associated with the disease sort of create an emotional terrain through which the oncology clinician must navigate.”

	Baile points out that oncologists deal with patients whose diseases are often incurable, or have low cure rates. As such, their job becomes two-fold: provide the level of treatment that offers hope of being cured and guiding and supporting them through their emotionally tumultuous cancer journey. The online videos, Baile says, are greared not only to help doctors tell the truth, but to respond in a way where the patient feels that no matter how bad the situation is, the clinician is going to stick with them.

	“There’s an attachment that cancer patients have with their treatment team, and it’s a very deep attachment,” Baile says. “Clinicians need to know how to take advantage of the relationship to promote the patient’s quality of life. How to provide the kind of education that is honest and yet hopeful. These are high-order skills that we’re talking about.”

	Baile believes that the healing process has a lot to do with a patient’s sense of security, and that sense of security is the cornerstone of trust. In the absence of both elements, patients are left feeling that the clinician is not taking an interest in them as a person. According to Baile, physicians often focus on curing, and while patients want to be cured, they’re really focused on healing and want their physicians to understand them as a person.

	Daniel Epner, MD, associate professor of general oncology at the MD Anderson Cancer Center, has participated in the center’s Oncotalk Teach 

, an educational research project that teaches clinicians how to impart communication skills in oncology to others. He explains that, “Far too few of us in medicine respond to patients’ emotions with empathic responses.”

	Epner currently teaches communication skills to oncology fellows and often refers back to the I*CARE Website and its video vignettes to further illustrate a point of discussion. He’s learned that just as empathy is important in the physician-patient relationship, it’s equally critical when teaching communication skills.

	“A fellow training in oncology is under a lot of stress,” Epner says. “They’re trying to learn a lot of technical, biomedical information. As teachers, responding to them with empathy, listening to them, and allowing them to explore and be reflective is very important. Those are the same skills we use with patients in other conversations.”

	Those conversations, such as the process of maintaining hope but balancing it with realism, are often difficult, says Epner. “Words are very important and powerful at that stage, but they really are important at every stage.”

	Baile sees the I*CARE Website as a form of distance learning. The modules are approved for CME credit, and the videos can be downloaded and used by clinicians teaching communication skills to medical students. Modules can be assigned for viewing before going on rounds to deliver bad news. The Website also features video interviews with key experts in the field of communication skills, as well as reflective exercises, and recently added a comprehensive bibliography. The actual dialogue used in the videos can be displayed on screen or downloaded and printed.

	“We were recently contacted by a clinician at a university in South Korea who is going to use [the transcript] to translate the video into Korean,” Baile says. “Anyone in another country who is interested in using the video can translate it into their own language. They can also take the transcript and edit it down if they want to use the scenario for a role play, such as in teaching medical students.”

	In addition, as part of the cancer center’s Achieving Communication Excellence lecture series, which is part of the I*CARE program, three new lectures will be videotaped and uploaded to the Website. The topics of the lectures include spirituality and communication, end-of-life discussions, and updates in communication skills research.

	“The Institute of Medicine has emphasized that communication skills are part and parcel of the care of the patient,” Baile says. “So now, the agencies that accredit all of the specialty fellowship programs, like oncology, have developed core competencies that every fellow must learn, and one is communication skills. There’s a push now to incorporate [communication] training into fellowship programs. But we’re still behind the times in doing this.”

	Biren Saraiya, MD, an assistant professor of medicine at the University of Medicine and Dentistry of New Jersey, is a graduate of MD Anderson’s Oncotalk Teach program, and believes that communication skills, especially for oncologists, are vitally important.

	“One of the things I tell all of my trainees is that any encounter could potentially be bad news for a patient, because bad news is very subjective,” Saraiya explains. “Having a methodology for how to communicate with patients is really important. If you have a framework to work off, and follow it all the time, it becomes a great skill set because it makes everything a bit easier.”

	Epner agrees, and points out that effective patient communication skills in oncology are more important than ever, in part because of the volume of information at patients’ fingertips. “When there’s so much information and it’s complex, patients need experts they trust to guide them through.”

	“So much emphasis in training has been placed on the medical aspect of things, and communication has taken a backseat,” adds Baile. “But for patients, it’s right on the front burner.”

Ed Rabinowitz is a veteran healthcare journalist based in Bangor, PA. 

Online Communication Tool Improves Physician-Patient Communication

	Proton therapy centers are being built around the country, and one of the companies leading this effort is ProCure, a company dedicated to improving the lives of patients with cancer by increasing access to proton therapy. Since 2005, ProCure has developed several centers and more are underway. Oncology Net Guide (ONG) recently had the opportunity to interview John Cameron, PhD, founder, chairman, and president of the ProCure Treatment Centers to gain insights on proton therapy from one of its biggest proponents.

ONG: Building proton beam centers is a costly endeavor, with start-up fees averaging $125 million. A considerable portion of the costs appears to arise from the need to build a large facility, measuring approximately 92,000 square feet, to house the giant particle accelerator. Has any progress been made in decreasing the size of these accelerators and in reducing costs? 

 The accelerator itself is generally not the largest component of the equipment. That, in fact, is the gantry that transports the proton beam around the patient. We already see new technology being implemented that will dramatically decrease both accelerator size and weight over the next 5 years with commensurate decrease in their cost. That said, proton therapy is a sophisticated therapy that requires a complex construction process, large precision instruments, and state-of-the-art information technology. ProCure has simplified and standardized the complex process of developing proton therapy and brought construction and start-up costs down by about 25% in just the past 3 years, and we’ve identified opportunities to bring these costs down even further. This is not unlike other sophisticated treatments where the cost of equipment, for example, will decrease as it is more widely used and developed.

	One of ProCure’s most significant advances, which has reduced the size and cost of our centers, is the development of a new treatment technology using two beam lines in the treatment room—the Inclined Beam Room. The Inclined Beam Room is only a fraction of the size of a gantry, the industry standard, allowing the footprint of ProCure Proton Therapy Centers to be much smaller at 60,000 square feet and less costly. The Inclined Beam Room can treat 80% of the tumors treated with a gantry at only 50% of the capital cost. The ProCure Proton Therapy Center in Oklahoma City is the first center in the world with this unique innovation.

ONG: Although the costs of administering proton therapy may be higher than that of conventional X-ray radiation, are there any long- term cost savings?

 When you discuss the cost of proton therapy and compare it with the most likely alternative, X-ray therapy, you must consider the cost of treating the short- and long- term side effects from conventional radiation therapy. These effects are not insignificant and all have an associated cost. Because proton therapy causes less damage to healthy tissue, side effects are greatly reduced. As a result, proton therapy limits productivity loss for both the worker and the employer. Short-term side effects such as nausea, vomiting, and loss of energy are reduced or eliminated, and workers can receive treatment and return to work the same day. Over the long-term, proton therapy reduces the chances of secondary cancers and tumor recurrence, saving costs associated with additional cancer treatment.

ONG: Do you think proton therapy will eventually replace conventional X-ray radiation therapy? 

 The downside of radiation is that it is inherently destructive; radiation damages healthy tissue on its way to the target and as it exits the body. As professor Herman Suit famously said many years ago, “there is never a good reason to irradiate healthy tissue.” Proton therapy is more precise and far less damaging. It is not yet a replacement for most radiation treatments, but rather an important and powerful complement to traditional therapy.

	Proton therapy also presents treatment options for some patients who cannot be treated with X-ray radiation. For example, proton therapy can be used to treat tumors that recur, while standard radiation therapy cannot, and when patients who have X-ray radiation reach a point where no further therapy can be tolerated, proton therapy may be an option. Patients prescribed chemotherapy may also benefit substantially from having concurrent proton radiation therapy because proton treatments are much less toxic than conventional therapy.

ONG: How does ProCure decide where to build a proton therapy center? 

	Dr Cameron: Our mission is to make proton therapy available in more locations so patients have access closer to home. We look for radiation oncology practices and hospitals or health systems that have a reputation for innovation and adopting advanced therapies and technologies, and are dedicated to finding the best and most appropriate medical care possible for their patients. The radiation oncologists and hospitals we have joined with have an overriding commitment to their cancer patients, which perfectly aligns with our mission.

ONG: Can you briefly discuss what went into building the ProCure Proton Therapy Center in Oklahoma City, which is the latest center to open? Were there any hurdles that had to be overcome and were any lessons learned along the way? 

 The ProCure Proton Therapy Center in Oklahoma City was built in a world-record 27 months, and we were able to reduce the cost of building the center through design and technological innovations. We accomplished this because our skilled team of proton therapy experts applied all of the “lessons learned” from their experience operating and building other proton and medical treatment facilities to the Oklahoma center. In turn, we’re already applying lessons learned from the Oklahoma center to further streamline the building process on our center under construction near Chicago and will do the same for our other centers under development in New Jersey, Michigan, and Florida.

	An obstacle other proton centers have encountered that we were able to avoid is staffing their centers and training those staff. Before we broke ground in Oklahoma City, we created the ProCure Training and Development Center (TDC), which opened in 2008 and is now the world’s only facility dedicated exclusively to proton therapy training. Other centers have had to use their treatment facilities to train their staff, which has delayed their ability to treat patients by many months. We trained the entire medical professional and administrative staff of the Oklahoma center at TDC before the treatment center was completed, allowing us to begin treating patients as soon as our equipment was commissioned.

	The TDC offers before-the-job training, ensuring that patient treatments can begin in an efficient and safe manner. The TDC provides fully simulated treatment rooms identical to those found in our proton center. Training includes a concentration on the necessary sophisticated technical skills and the “softer” skills, such as empathy training, that provide comfort and assurance to patients. The TDC also has treatment planning areas, an immobilization device development area, and lecture rooms.

ONG: Have you encountered any patients reluctant to receive proton therapy, namely, do some think of this modality as experimental? 

 We have not found this to be the case. Patients seek proton therapy because they are referred by their physicians or learn about protons through their own research and decide to explore it as an option. Proton therapy has been used for more than 50 years, and it was endorsed by the Centers for Medicare and Medicaid almost a decade ago; these facts are reported in most of the literature and Websites that discuss protons. This therapy is also covered by many insurance plans, Medicare, and state Medicaid plans, which is another reassurance for patients.

	The major issue we’ve faced is that the majority of patients who could benefit from this highly effective cancer treatment aren’t able to receive it because treatment availability is still limited, but this is an issue we are working on resolving. We are also committed to progressing the knowledge and research regarding proton therapy, and short-term and long-term outcome data will be collected for every patient treated at a ProCure center.

ONG:What should medical oncologists know about proton beam therapy? 

 Proton therapy has proven efficacy for the treatment of specific solid tumors and provides an additional treatment option for patients and clinicians. Research is also underway for an expanding numbers of tumors.

	Because proton therapy is characterized by less radiation being delivered to healthy tissue and critical structures adjacent to the treatment volume, as well as the ability to deposit a larger dose in the targeted volume, its most significant benefits are less short- and long-term side effects versus X-ray radiation. Medical oncologists, in particular, should be aware that patients prescribed chemotherapy can have proton therapy because these treatments are much less toxic than standard radiation, enabling proton treatment to be more readily used concurrently with chemotherapy.

	These factors can result in a number of benefits, including improved tumor control, reduced incidence of secondary tumors, fewer treatment- related short- and long-term side effects, and extended survival times.

ONG: Has the research shown a survival benefit with proton therapy versus X-ray therapy? 

 Because radiation oncology is a physical science, the benefits of one versus the other can be modeled to identify the exposure of radiation to healthy tissue. Research at 

 has shown that proton therapy may decrease the rates of secondary radiation-associated cancer by between 26% and 39% compared with intensity-modulated radiation therapy.

 from Massachusetts General Hospital found significantly lower secondary cancer rates with a combination of X-ray radiation and protons (6.4%) compared with the national average with X-rays (12.8%). In addition, patients who received only proton therapy had no secondary malignancies.

Proton therapy centers are being built around the country, and one of the companies leading this effort is ProCure, a company dedicated to improving the lives of patients with cancer by increasing access to proton therapy. Since 2005, ProCure has developed several centers and more are underway. 

An Interview with ProCure Treatment Centers' Founder:  John Cameron, PhD

	Radiation therapy has been used to treat cancer for more than 100 years, and was made possible by the discovery of X-rays in 1895 by German physicist Wilhelm Conrad Röntgen, which allowed tumors to be detected more easily and noninvasively. In the early 1900s, the field of radiation therapy began to expand, especially after Marie Curie discovered the radioactive elements polonium and radium; however, once the ill effects of radium became apparent in the mid-1900s, radium isotopes were largely replaced by cobalt and caesium, which were found to be safer and more effective.

	The first clinical use of X-ray radiation therapy was undertaken in 1937 to treat a patient with leukemia at the University of California at Berkeley. Since then, there have been considerable advances in radiation therapy. Some of the most recent include three-dimensional conformal radiation therapy, intensity-modulated radiation therapy, stereotactic radiotherapy, brachytherapy, and radioimmunotherapy, all of which have improved radiation targeting by limiting radiation exposure of healthy tissues. One of the most promising recent advances, however, is the use of proton beam therapy. There are currently seven institutions in the United States that offer proton therapy, and several more centers are in development.

	Protons are heavy, positively charged subatomic particles that were first discovered by British physicist Ernest Rutherford in 1919. Proton therapy is an external beam radiotherapy in which protons are accelerated in a particle accelerator to almost the speed of light and then slowed down to the target speed before hitting the tissues. Unlike conventional radiation therapy, which uses photons, protons can be manipulated to release their energy at a precise point. The depth of their penetration into the human body depends on how much energy the protons acquire, which is carefully calculated before therapy is administered. The peak of the radiation dose, referred to as the Bragg Peak, conforms to the back of the tumor; thus, almost no radiation is administered beyond that point, ensuring the healthy tissue behind the tumor is spared. Although the healthy tissue in front of the tumor is exposed to the protons, the treatment conforms so closely to the tumor that the effects of this exposure are minimized, and the procedure is painless and without side effects in most patients.

	In contrast to proton therapy, conventional photon therapy does not permit the irradiation pattern to conform to the cancer as accurately; thus, the surrounding healthy tissues and organs often receive a similar dose and may become damaged in the process. To spare healthy tissues and prevent any untoward side effects, radiation oncologists often administer a lower dose of photons than is desired, which may reduce the efficacy of treatment. Because of how well protons conform to the tumor, higher doses of radiation can be used to control and manage the cancer while significantly reducing damage to healthy tissues and vital organs. Proton beam therapy also does not affect the bone marrow, allowing chemotherapy agents to be used that previously could not be administered in the setting of radiation therapy; thus, this modality expands the available treatment options for certain patients.

	While it is unclear whether proton therapy offers a survival benefit compared with photon therapy, a study presented in 2008 at the 50th Annual Meeting of the American Society for Radiation Oncology (formerly known as the American Society for Therapeutic Radiology and Oncology, but still referred to as ASTRO) in Boston reported that patients treated with proton therapy had a two-fold decreased risk of developing a secondary cancer compared with those treated with standard photon therapy. This may be an especially important finding for pediatric patients, who are at greater risk of developing secondary tumors.

WHICH PATIENTS BENEFIT FROM PROTON THERAPY?

	Proton therapy has been found to be effective in treating brain, head and neck, central nervous system, lung, and prostate tumors, and with considerably fewer side effects than conventional photon therapy. For instance, a 2006 report by Metz found that less than 2% of patients who received proton therapy for head and neck cancer became blind versus 15% of those who received conventional radiotherapy. This modality may also be beneficial in treating tumors that are unresectable or close to vital organs, and its precise targeting offers considerable benefits to pediatric patients, who are especially sensitive to the effects of radiation.

	As the technology behind proton therapy continues to evolve, more tumors will become treatable using this modality. In February 2009, the University of Florida Proton Therapy Institute in Jacksonville announced the availability of uniform scanning, which allows the proton beam to cover a wider treatment area and penetrate deeper into the body than the more commonly used scattering method. As a result, the institution is now able to treat sarcomas larger than 9.4 inches and prostate cancer in patients with a hip circumference of more than 50 inches.

	Because of the limited number of proton treatment facilities worldwide, physicians have focused on using the therapy for a small number of patients with diagnoses that make proton therapy especially beneficial, such as cancers and other tumors in children and tumors that are near vital organs or structures. The indications for proton therapy will continue to expand as more treatment centers open and become involved in clinical research. Currently, numerous clinical trials are being conducted to investigate proton therapy, including for rarer cancers, such as chondrosarcomas. See the sidebar on the right for a list of some of the proton therapy clinical trials that are currently recruiting patients.

	Building a proton therapy center is costly, ranging from $100 to $250 million, and once up and running, there are substantial operating costs. It is estimated that a $125 million facility may generate operating costs between $15 million and $25 million annually. These facilities require a tremendous amount of space, approximately that of a football field, contributing to the cost. Because of the expense of building and running these facilities, the costs of administering this therapy are substantially higher than that of conventional radiotherapy. Currently, one treatment can range from $1500 to $2000, and patients typically require between 20 and 40 treatments, depending on the location and size of the tumor; thus, complete treatment may range from $30,000 to $80,000. Many US insurance providers cover proton therapy, as does the US Medicare program and many state Medicaid programs. It is also anticipated that the costs of treatment will go down as more centers are built.

	The latest proton therapy center to come on the scene is the ProCure Proton Therapy Center in Oklahoma City, which was built in just 27 months. The facility opened its doors to patients on July 8, 2009, and this marks the first time proton therapy will be available in a community hospital setting, outside of an academic center. The ProCure facility measures 60,000 square feet and is the first to feature inclined beam rooms, which allow the proton beam to be delivered from two angles (horizontal and 60 degrees inclined from horizontal), replacing the need for multiple full-gantry treatment rooms. These rooms allow 80% of tumors to be treated without a gantry, cutting treatment costs by 50%.

	Other innovations at the Oklahoma facility include the use of image-guided radiotherapy and a robotic patient positioning system (PPS). The PPS is a computer-controlled robotic system that moves patients precisely into the treatment position, eliminating the need to create body pods to hold patients in place during treatment. This system received FDA approval in spring 2009, and the Oklahoma center is the first one to use this technology; however, ProCure has shared these innovations with IBA in Belgium and other centers. For more on this center and proton therapy, turn to page 38 to read our interview with John Cameron, PhD, founder of the ProCure Treatment Centers.

	More than 60,000 people worldwide have received proton therapy at centers in the United States, Europe, and Asia. While it is estimated that more than 250,000 US patients with cancer may benefit from proton therapy, the centers that are currently in operation can only handle about 6,000 treatment slots per year; however, as more facilities continue to open, the technology continues to improve, and costs are cut, considerably more patients will be able to fight their cancer using the power of protons, another effective weapon in the oncology arsenal and a ray of hope for patients.

Radiation therapy has been used to treat cancer for more than 100 years, and was made possible by the discovery of X-rays in 1895 by German physicist Wilhelm Conrad RÃ¶ntgen, which allowed tumors to be detected more easily and noninvasively.

September 2009 | Oncology Live®

5-FU Dose Optimization: Another Step Towards Personalizing Cancer Care

Collaborative Effort to Address the Needs of Cancer Survivors

Online Communication Tool Improves Physician-Patient Communication

An Interview with ProCure Treatment Centers' Founder: John Cameron, PhD

PROTONS: A ray of hope in oncology