Melissa Knopper

Five years ago, Alvaro Martinez, MD, a radiation oncologist at Beaumont Hospitals in Royal Oak, Michigan, was attending a medical conference in Dearborn when he happened to wander into the wrong conference room. There, he found a group of Ford Motor Company engineers talking about how to check for defects in engine blocks with CT (computed tomography) scans. 

, who had been looking for a way to improve radiation therapy, had a brainstorm. Today, Beaumont cancer patients are benefiting from that idea: The $3.3 million Omnibeam is helping doctors treat hard-to-reach tumors deep inside the body. The machine combines a powerful CT scan with robotic technology that automatically adjusts for movement—the way a patient’s chest rises and falls while breathing, for example.

 radiologists like Frank Vicini, MD, treat a tumor with much more confidence than they have in the past. “The Omnibeam’s robotic couch moves the patient in unison with the beam,” Vicini says. “So it really affords you tremendous precision.”

In the past, radiation oncologists radiated a broad volume of tissue—both healthy and cancerous&mdash;to make sure they didn’t miss any stray cancer cells, explains Robert Kuske, MD, a 

, radiation oncologist. In the process, healthy tissues were at risk for side effects or complications just because they were in the way of the radiation beam. Treating cancer in the pancreas, for example, could cause bowel problems.

Researchers knew they needed to innovate—to hit their targets more precisely and avoid excess damage. Doing so would cut down on side effects for the patient and allow dose escalation to prevent recurrence.

Now, cancer patients are seeing the benefits of cutting-edge (although costly) radiation technology. Instead of relying solely

external treatments that send radiation into the body from an outside source, radiation oncologists now have newer techniques that target cancer cells from inside the body. Plus, new imaging techniques and devices, as well as various forms of energy, are allowing physicians to deliver radiation in a more precise way that is making life better for patients.

“[These innovations] bring a decrease in side effects, an increase in quality of life. And it’s more user-friendly for the patients,” Kuske says. “It is indeed a very exciting time.”

Research has pointed to the great need for new and better technology. One study of 803 patients with cancer of the prostate, head and neck, or brain showed patients given external beam radiation therapy routinely received the wrong dose. Results showed 46 percent of the patients were given 10 percent more radiation than physicians had intended, while 63 percent received 10 percent less than the prescribed dose.

Plus, the long-term side effects of external beam’s broad coverage approach can be serious, especially for patients with cancer in the left breast. “In the past, the radiation beam penetrated the anterior surface of the heart in order to cover the entire left breast,” Kuske explains. “It exposed a coronary artery to full doses of radiation, increasing the risk of fatal heart attacks 10 to 15 years later.”

These challenges led to a new way of thinking about radiation treatment, starting with three-dimensional conformal radiation therapy (3-D CRT), the first innovation to address the need for a more precise dose. Using digital imaging—typically with computerized tomography (CT)&mdash;the treatment team creates a three-dimensional image of a tumor inside the patient’s body. A virtual computer model lets technicians try out different angles and different doses to make sure they will be able to hit the target without damaging healthy tissue. Finally, they aim several powerful beams of radiation at the tumor. By attacking it from different angles, they decrease the chance the cancer will return.

Intensity-modulated radiation therapy (IMRT) takes 3-D CRT a step further. With IMRT, physicians can choose a different number of beams and set them at different angles, but they can also adjust the intensity of the dose. When treating prostate cancer with IMRT, for example, radiation oncologists use as many as 36 beams (compared with four using traditional techniques) to match the shape of the prostate and miss the bladder, avoiding future problems with incontinence. One example of IMRT is TomoTherapy, a CT-like machine with a radiation source that moves around the patient in a circle as it hits the tumor with thousands of tiny beams, or beamlets.

Cox, MD, head of the radiation oncology division at 

seen positive results from this new 3-D technology, especially in lung cancer. Cox says the facility’s three-year survival rate for non-small cell lung cancer has approximately doubled since 3-D CRT and IMRT became available. Three-dimensional radiation therapy is also particularly suited to prostate cancer and certain brain tumors.

Many of the nation’s largest cancer centers are investing millions of dollars in similar machines, such as CyberKnife and Gamma Knife. With this technology, known as stereotactic radiosurgery, surgeons use high-dose X-ray beams or laser beams to treat tumors without making an actual incision. The beams are guided by digital imaging. These techniques are also used for patients who need surgery in areas such as the brain and spine.

What we're seeing with these advances and new technologies is we can give higher doses and get better tumor control with less side effects.

The exciting thing about all of these new delivery methods, says Cox, is they can be used with different types of energy sources. For example, external beam radiation therapy uses both X-rays and electrons. But now, more facilities, such as M.D. Anderson, are experimenting with proton beams as well.

The benefits of proton beams have been clear for many years now, Cox says, but it hasn’t been possible to transfer the technology from physics research facilities to hospitals and cancer centers until recently. M.D. Anderson invested $125 million to build its proton therapy center, which opened in 2006, and Cox feels it was well worth it.

“What we’re seeing with these advances and new technologies is we can give higher doses and get better tumor control with less side effects,” he says. “We wanted to chart a course for the future, not wait for the future to catch up with us.”

With traditional external beam radiation, X-ray beams hit the target but then pass all the way through the body, leaving a trail of damage behind them, Cox explains. Protons, by contrast, hit the tumor and stop, making proton beam therapy much safer for pediatric cancer patients and for patients with brain, prostate, or lung cancer. Pediatric patients, for example, have less risk of secondary cancers, infertility, and bone deformity later in life. Avoiding normal tissue is important in children, Cox says, because growing structures, like bone and soft tissue, are very susceptible to radiation damage.

A typical complication of external beam radiation for lung cancer is pneumonitis (inflammation of lung tissue), a potentially life-threatening problem. By using IMRT, M.D. 

 physicians cut the rate of pneumonitis to 9 percent. Now, with proton therapy, Cox has seen no cases of pneumonitis so far. “It’s hitting the target and avoiding normal lungs better,” he says.

Besides M.D. Anderson, at least five other hospital-based facilities in the 

 offer proton therapy, and nearly a dozen new centers are in the works. Beaumont Hospitals just received state approval to build one on its 

Heat and light are other energy sources being explored as treatment. Protons and electrons are examples of ionizing radiation, while heat and photodynamic therapy are non-ionizing, meaning they cannot disrupt chemical bonds and cause DNA mutations.

Through various studies, researchers have shown the therapeutic use of heat, or hyperthermia, has an additive effect in radiation. Health care providers increase the body temperature by using energy sources such as microwaves, ultrasound, or radiofrequency energy. While studies are not conclusive on the benefits of hyperthermia, some believe it can alter the proteins in cancer cells and make them more susceptible to traditional radiation therapy.

Photodynamic, or light, therapy often uses lasers, fiber optics, and light-sensitive drugs, to treat a variety of cancers, including skin, brain, and gynecologic. Photofrin (porfimer), a drug used in photodynamic therapy, is absorbed by cancer cells and becomes briefly activated when exposed to light. The cancer cells are killed, and damage to normal cells is minimized. Light sensitivity can be a side effect of Photofrin, so patients are usually advised to avoid sunlight until the drug is out of the body.

View Illustration: Radiation Manipulation

While external approaches began to take shape, physicians also started to look for internal solutions. Intraoperative radiation therapy is a newer type of internal radiation that helps patients who have a tumor that cannot be completely removed because of its location in the body (near the heart, optic nerve, or brain). During surgery to remove the tumor, radiologists aim an electron beam at the remainder of the tumor.

Physicians can also place radioactive material directly inside the body that emits a type of radiation that only travels a few millimeters, a technique called brachytherapy. 

’s Vicini were among those who experimented with placing tiny pellets of radiation, or “radioactive seeds,” directly into the surgical cavity after tumor removal.

Brachytherapy has led to advances in prostate cancer, such as TheraSeed, and multicatheter interstitial brachytherapy for breast cancer. More modern breast cancer techniques include MammoSite (see illustration), Contura balloon catheters, and expandable, single-entry strut catheter devices.

Another form of brachytherapy called radioembolization uses tiny glass spheres smaller than a human hair that are filled with radioactive compounds. The tiny bubbles can move into the circulatory system and shut down the blood supply to a tumor deep inside the liver.

Brachytherapy, however, is not a new science, Kuske points out. The British surgeon Sir Geoffrey Keynes (younger brother of economist John Maynard Keynes) offered patients brachytherapy for several years in the 1920s when the only delivery choice was radium seeds or needles, Kuske says.

Keynes’ work with this new technique halted during World War II, when fears that his lab would be bombed caused him to bury all of his radioactive -materials in the English countryside.

Since then, Kuske, Vicini, and others have turned to brachytherapy, which they consider the ultimate precision conformal radiation delivery method, in their search for a potentially better way to treat breast cancer. Kuske realized physicians were already using an abbreviated form of brachytherapy by giving patients a “boost” with radioactive needles to intensify external beam radiation treatment at the lumpectomy site.

“In 1991, we got the idea to do the whole thing with brachytherapy for select breast cancers,” says Kuske, who was working in 

 at the time. “With the help of two prominent biologists, we figured out the dose, and the rest is history.”

Kuske estimates half of his early-stage breast cancer patients opt for lumpectomy and partial breast irradiation, a five-day alternative to conventional six-week external beam whole breast irradiation. In partial breast irradiation, physicians typically use brachytherapy as the method for delivering radiation.

Partial breast irradiation, however, remains open to debate as researchers and physicians anticipate definitive data from several phase III clinical trials now under way. Current data suggest the technique is as effective as standard external beam whole breast radiation, but the small number of patients followed for limited lengths of time hinders a definitive conclusion.

Another new trend in breast cancer is hypofractionated radiation, which gives patients the option of taking a stronger dose of radiation in about half the time as the standard treatment schedule. Most physicians use external beam radiation for this type of treatment.

Hypofractionated radiation has been popular in the 

 and Europe for years, but is just now catching on in the 

. A study presented at last year’s San Antonio Breast Cancer Symposium revealed 12-year data that showed the recurrence rate for early-stage breast cancer patients was about the same with hypofractionated radiation (6.7 percent) compared with the standard schedule (6.2 percent). Despite the appeal of more convenient treatment, American physicians are still concerned about the cardiac risks of irradiating the left breast with strong doses.

They borrowed ideas from the auto industry and revived an old technique from the past, and now, radiation oncologists must continue to find new energy sources and better ways to deliver radiation therapy. The buzzword for the future is synergy—combining radiation with other treatment methods and other specialties to shut down cancer growth from different angles. 

"Across the spectrum of many types of cancer, we're now going to more targeted therapy," Kuske says. "We're targeting the dose just to the tissues at risk. In other words, we're getting better at avoiding collateral damage."

Across the spectrum of many types of cancer, we're now going to more targeted therapy. We're targeting the dose just to the tissues at risk. In other words, we're getting better at avoiding collateral damage.

Articles

Technology propels radiation therapy to a new status: targeted therapy. 

A Direct Hit

While the field of radiation has certainly seen many exciting advances in the past decade, experts like 

, chair of radiation oncology at the University of Texas Southwestern Medical Center at 

, look forward to even more innovations on the horizon. Most of the coming changes, he says, involve combining new technology with other therapies.

“A cancer is made up of very heterogeneous tumor cell population, which often makes it difficult to eradicate with one drug or modality,” Choy says. “So we need to use agents or modalities that have synergistic effects.”

In the past, radiation therapy was the main modality to treat lung cancer, Choy’s specialty. Later, physicians combined chemotherapy with radiation therapy, which requires close collaboration between medical oncologists and radiation oncologists.

Choy is a leader in looking for ways to use chemotherapy and radiation, along with biological therapies, in a discerning way that helps physicians outwit the cancer. In some cases, cancer cells have the ability to repair themselves after chemotherapy. Others can’t survive chemotherapy, but are less vulnerable to radiation.

“Radiation works on different cell populations,” Choy explains. “Some cells are more resistant, some are more susceptible to radiation.”

Cells that are hypoxic (have a shortage of oxygen) are more resistant to radiation, Choy says, and some cancer cells develop resistance to radiation therapy over time. Others are just intrinsically resistant, he adds. A study from the 

 showed 46 percent of breast cancer stem cells survived radiation treatment compared with 20 percent of normal breast cancer cells. The UCLA researchers suggested radiation may activate a signaling pathway that alerts the cancer stem cells to start repairing themselves.

If oncologists can better coordinate their efforts so that chemotherapy and radiation shut down the cancer cells with a synergistic effect, Choy believes they can make an impact on cancer cells’ ability to survive.

An exciting example of this synergy is the monoclonal antibody Erbitux (cetuximab) combined with radiation therapy. While effective on its own as an epidermal growth factor receptor inhibitor, studies show Erbitux makes cancer cells less likely to recover after radiation. It has been especially helpful in lung and head and neck cancers. Choy’s research has looked at targeted therapies, such as Erbitux, as a potential treatment for non-small cell lung cancer.

Success in fighting the cancer war depends on how well we kill the cancer cells while minimizing the [side effects]," Choy says. "I believe the comination of radiation, chemotherapy, and biological therapy will maximize the chance we'll win."

Radiation oncologist Hak Choy, MD, became a leader in the cancer field when he began looking for ways to combine radiation, chemotherapy, and targeted agents against cancer.

Hak Choy: The Combined Approach

Detroit-area radiation oncologist Frank Vicini, MD, would often see women come down from the upper peninsula of 

"In some cases when patients have to travel a long distance, it can be quite a concern to come back for 25 or 30 treatments of radiation therapy,” Vicini says.

Since many of the patients could not afford to stay in a hotel that long and didn’t want to travel, some opted for a mastectomy at their local hospital, even though they could have had a lumpectomy and radiation. The expense and inconvenience presented a barrier, Vicini says.

Concerned, he started looking into better alternatives for these women. That’s when he learned about accelerated partial breast irradiation.

The idea, explains Vicini, was to give a more intense dose of radiation in a more localized spot for a shorter period of time. Today, women who qualify can finish treatment in five days instead of five or six weeks.

Vicini and Robert Kuske, MD, a radiation oncologist from 

, are pioneers of accelerated and other forms of partial breast irradiation. Their initial research showed it has the same effectiveness as whole breast radiation, and other institutions matched their outcomes. After a successful National Radiation Therapy Oncology Group phase II trial, the National Cancer Institute is now sponsoring a randomized head-to-head comparison to the six-week standard to confirm that local recurrence rates are similar.

Some radiation oncologists, including Lori Pierce, MD, from the 

, urge caution until the NCI study results are available. Pierce says it pays for women to get all of the information and make a careful decision.

“It’s important when physicians talk with patients they be very clear about what we know and what we don’t know, so they can make a good decision,” she says.

One unresolved question, for example, is whether it is possible for women who do have a recurrence to have additional radiation to the same breast. This will most likely be decided on a case-by-case basis and will depend upon the dose used and the volume of breast and other tissues previously irradiated to determine whether additional treatment can be safely tolerated, Pierce says.

Kuske and Vicini are two of the leaders in the all-important phase III randomized trial.

"We're doing due diligence to definitively establish whether this is an equivalent standard of care," Vicini says. While partial breast irradiation is already popular at many hospitals across the country, Vicini says, "we have to do the right thing scientifically before this is adopted on a wide scale."

A shorter schedule of radiation therapy may be more convenient and cost effective for women with early-stage breast cancer.

Short Schedule Just as Good in the Long Run?

In the chaos and intensity that surrounds a new cancer diagnosis, everyone tends to focus all of their care and concern on the patient. Too often, medical staff and relatives forget to stop and ask the family caregiver how they are doing.

While caregivers tend to brush their own needs aside, experts warn that completely selfless devotion can backfire. A study in the Journal of the American Medical Association found that elderly caregivers have a 63 percent higher mortality rate than their peers. And new research highlights the importance of the caregiver's well-being. It turns out, the health and mental outlook of the caregiver can impact a cancer patient's survival and quality of life.

Take a look at some of the typical "side effects" cancer caregivers tend to experience:

 showed women who cared for their husbands who had prostate cancer experienced depression at twice the rate of the cancer patients themselves. Caring for someone full-time can lead to feelings of panic, despair, and isolation. And after the initial crisis of diagnosis, surgery, and chemotherapy or radiation, there's a lingering worry that the cancer could return. Reach out to friends and family, online chat groups, and support organizations to help reduce the feelings of isolation.

If after talking with friends and family or trying exercise and other stress reduction techniques doesn’t help , it may be time to see a therapist or talk to a doctor. This may be the first time you have ever felt truly depressed, but there is no shame in asking a professional to help pull you out of it.

 Getting up in the night to care for a sick person, offer pain medication, or just listen for changes in breathing can wreak havoc on normal sleep patterns. Sometimes this wakeful type of sleep can become a habit and leave caregivers exhausted during the day. Other times, caregivers may find themselves wide awake in the middle of the night, feeling overwhelmed by fears and worries.

To overcome insomnia, sleep experts suggest everything from guided imagery and relaxation techniques to acupuncture and even warm milk, which contains a sleep-inducing compound called tryptophan. Cutting back on late afternoon coffee breaks and boosting your exercise, especially yoga, can also help caregivers sleep better. Sometimes it helps to write down your worries, and release them for the day, before heading to bed. If all else fails, it may be time to talk to the doctor about a non-addictive sleep aid.

 The constant stress of caregiving can make you more vulnerable to getting sick. Stress can make your back and shoulders tense, and lead to more aches and pains than usual. Experts at the Family Caregiver Alliance remind us to listen to the airline attendant who says to put on your own oxygen mask before you help someone else. That means taking a look at your stress level as a caregiver and trying to prevent burnout before it hits. Make a list of what triggers your stress right now. Then make another list of steps you could take to reduce that stress. As former First Lady and caregiver advocate Rosalynn Carter says, you can't be much help to your sick relative if you don't take care of your own needs—both physical and emotional.

Experts who study the art of caregiving offer the following common-sense solutions to help caregivers manage their stress and refuel:

 American Cancer Society researcher Youngmee Kim, PhD, calls it "benefit finding." Other researchers label it a "sense of mastery." If you can take your experience with cancer, even as a caregiver rather than a patient, and learn from it, you will have less depression and anxiety. Cancer caregiving can help you find more meaning in your life and focus on the right priorities into the future. How to better develop this sense of mastery? Work on your personal growth. Participate in an art therapy workshop for cancer patients and spouses, buy a new journal and write your way to the answers, talk with a counselor, or lean on your faith.

Others delve into the cancer diagnosis, trying to learn everything possible about the patient's condition. This gives caregivers a sense of control and helps them to be better patient advocates. If you accept your role as caregiver, and approach it like a professional, it can be a very empowering experience.

 Support from family and friends is key. Everyone knows this, but it's not always easy, especially for caregivers who live in remote rural areas. Advocates at the Well Spouse Association got around this barrier by sending "round robin"-style letters to caregivers who lived in isolated settings and couldn't make it to a local support group. Caringbridge.com is another nice resource for family members who are scattered around the country but want to stay close. Otherwise, support groups for cancer patients and caregivers are pretty easy to find through local hospitals and the American Cancer Society. Join one. It makes a huge difference to feel you're not the only one going through something hard.

 As the primary caregiver, you may bump into a friend or neighbor who asks, "What can I do to help?" Veteran caregivers offer this suggestion: Always keep a list in your pocket. That way, you can pull it out and sign them up to sit by your relative's bedside so you can get out for a nice walk, attend religious services, take a yoga class, or get a massage. For other shy types, there are websites such as Lotsa Helping Hands that allow caregivers to set up a system with calendars and online organizing tools so friends and family can jump in and help without even being asked.

If friends or relatives are not available to step in for a few hours, hire someone, or find adult day care. The U.S. Administration on Aging offers a national database of elder care providers, called Eldercare Locator.

 Most often, when a person is diagnosed with cancer, it's the spouse who takes over the caregiving. American Cancer Society research shows husbands and wives can affect each other in profound ways in this new relationship (as patient and caregiver). And it goes both ways. First, they discovered wives hold themselves up to impossibly high standards as caregivers. They get stressed out, try to do too much, and rarely make time for themselves. The study showed this had a negative effect on the husband's ability to heal. Instead, the husband absorbed these negative feelings and felt guilty about putting his wife through so much.

Meanwhile, the ACS study found male caregivers also affect their wives, but in a different way. A group of women with breast cancer said their husbands would try to ease their worries and fears by minimizing them and offering "quick fix" solutions. While the husband wanted to help, the wives perceived this as an uncaring attitude. Most of the women said they just wanted someone to listen and give them a hug. As a result of this study, the ACS may soon offer a special course for male cancer caregivers that will teach empathic listening and open communication.

With everything they have to do in a day, caregivers often neglect basic health maintenance. Sometimes caregivers get in the habit of putting themselves last. If that's the case for you, try thinking of it a different way—if you can see it as giving a gift to the person you are caring for, it might be easier to make time each day for good nutrition and exercise. Caregiver groups offer the following reminders to help caregivers take better care of their personal health:

> Make sure you add some fruits and vegetables to your diet each day.

> Eat three meals a day, and guard against weight loss.

> Shoot for eight hours of sleep per night, when possible.

> Exercise or go for a walk every day, even if only for 10 to 15 minutes. Studies show exercising four times a week helps caregivers sleep better, prevent heart disease and high blood pressure, and stave off depression.

> Line up help so you can keep your regular appointments for dental cleanings, health screenings, and annual check-ups.

> Get a flu shot so you don't get stuck being too sick to be a caregiver or put your loved one in danger of getting sick themselves.

> Make room for humor. Keep in touch with friends who make you laugh; rent a funny movie now and then.

> Keep up with social groups, such as a book club or a softball team. These are important ways to combat stress. Schedule regular times to socialize with friends and family.

As a caregiver, it's common to get so absorbed in your new role that you lose your own identity. Neglecting your personal needs is easy to do, but avoiding this common pitfall is key, both for the patient’s well-being and your own. Remember, you are still a person in your own right and it's not shameful to care for yourself before turning back to your caregiver duties. In fact, it's one of the most important ways you can help another person.

How and why caregivers should care for themselves.

Melissa Knopper

A Direct Hit

Hak Choy: The Combined Approach

Short Schedule Just as Good in the Long Run?

Taking Care of Yourself

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