Maureen Salamon

After James Levy finished his high-dose-rate (HDR) brachytherapy to treat his localized prostate cancer, he celebrated by getting a tattoo that included the StandUp2Cancer logo, the date his treatment ended and the word “radioactive.” It was his way of acknowledging his successful treatment with this relatively new approach.

“I’m a big fan of HDR brachytherapy,” says Levy, of Richmond, Va. “I went in Friday and was back at work on Monday. There was nothing to it.”

HDR brachytherapy, which involves placing strong sources of radioactivity in or near the cancerous tissue for a few minutes and then removing them, joins other, more established forms of radiation as a treatment option.

These techniques include one other type of brachytherapy and many forms of external beam radiation therapy (EBRT), which sends beams of radiation into the prostate from outside the body. In addition, for men whose prostate cancer has metastasized to the bone, a fairly new radiopharmaceutical is available. These approaches give patients a variety of choices if they select radiation treatment as either a first-line or follow-up therapy.

The common variable that internal and external radiation share is their increasing ability to deliver higher doses to the prostate while reducing exposure to nearby healthy tissues. Nonetheless, the treatments can cause side effects, including temporary fatigue or later development of permanent urinary incontinence, bowel problems and erectile dysfunction, among others.

For Levy, 57, who completed treatment about a year ago, side effects have not been an issue. “I’ve had none of the common long-term effects, like incontinence, erectile dysfunction or bowel issues,” says Levy. This is likely because of HDR’s ability to direct radiation specifically at the tumor and avoid nearby tissue and organs — and its short duration.

To treat his localized prostate cancer, James Levy chose high-dose-rate brachytherapy, and has not experienced any long-term side effects. [Photo by Liza Bishop, VCU Massey Cancer Center]

While that outcome is compelling, HDR may not be right for everyone. In fact, sifting through possibilities to arrive at the best radiation option for each patient can be challenging, says James B. Yu, a radiation oncologist at Yale University School of Medicine in New Haven, Conn. The decision, he says, is as individual as the man and his cancer.

“It depends on what you’re looking at — cure rates or complications,” he says. “Patients care about some complications more than others, such as erectile dysfunction, so the choice of treatment is intensely personal.”

Questions about the relative value of newer radiation methods may, in particular, give men pause.

For instance, in administering EBRT, “Physicians are looking at shortening the number of radiation treatments by increasing the dose per treatment,” Yu explains. He says there continues to be concern that giving more intense radiation treatments, even if there aren’t as many, could be more toxic overall. Adding to the confusion is that current research is mixed, highlighting “the complexity of comparing these treatments and saying that one is better than the other.”

Yu urges patients to learn as much as they can about the pros and cons of various treatments before making a decision, and to discuss any questions they might have with their health care providers. Levy agrees, adding that “the Internet makes it possible to become really well-informed.”

For men with localized prostate cancer (meaning it hasn’t spread outside the gland), often the first step after diagnosis is choosing between active surveillance (particularly for lower-grade tumors, as indicated by the level of prostate-specific antigen [PSA] in a man’s blood and the Gleason score doctors use to describe aggressiveness); surgery to remove the prostate gland (called a radical prostatectomy), or radiation therapy. If a man has localized prostate cancer and plans to undergo treatment, he should know that surgery and radiation are considered equally effective when it comes to preventing the advancement of the disease, according to the American Cancer Society (ACS).

One option for men with locally advanced prostate cancer (in which lymph nodes or other nearby tissues are involved) is radiation therapy plus hormonal therapy, which several studies have shown is more effective at fighting the cancer than hormonal therapy alone. In addition, men with this condition and a higher risk of recurrence should be informed that radiation therapy after a radical prostatectomy decreases their risk of cancer recurrence or progression, according to national guidelines issued in May 2013. Issued jointly by the American Society for Radiation Oncology and the American Urological Association, the guidelines also state that doctors should offer “salvage radiotherapy” to patients whose PSA levels rise, or who have a local recurrence after prostatectomy but show no evidence of distant metastases.

In 2015, the National Comprehensive Cancer Network (NCCN) issued new guidelines for patients. These guidelines recommend EBRT as a staple of treatment for men with various stages of the disease: as a first-line treatment for those at low risk for developing metastatic disease and who are expected to live 10 years after diagnosis; as a first-line or adjuvant therapy for many categories of men at intermediate risk, and for many groups of men with high-risk disease.

Most radiation options fall under the umbrella of EBRT, which is typically administered over a seven- to nine-week period, according to the ACS. Among EBRT therapies, intensity modulated radiation therapy (IMRT) is the most common and has been adopted extensively over the past 15 years. This approach uses a machine that moves around the patient, shaping the beams and aiming them from several angles. In this way, the dose of radiation can be adjusted, directing higher doses to the places where there are cancerous cells.

Other high-tech options include three-dimensional conformal radiation therapy (3D-CRT), image-guided radiation therapy and intensity-modulated arc therapy. The shared element among these therapies is a careful mapping of the exact size, shape and location of the prostate gland and tumor using imaging tests, such as computed tomography and magnetic resonance imaging scans or X-rays. This information helps doctors determine precisely where to aim higher and lower doses of radiation for maximum effectiveness and minimum side effects. One recent comparative study showed that IMRT offers a disease-control advantage over 3D-CRT.

Stereotactic body radiation therapy (SBRT), which is often referred to by the names of the machines that administer the radiation, including CyberKnife, Gamma Knife and X-Knife, is a form of EBRT that delivers large doses of radiation to the prostate. Although the benefit of SBRT is that its entire treatment course is days and not several weeks, some studies have shown side effects to be worse with this form of therapy.

Another promising, yet controversial, form of EBRT is proton beam therapy, which aims protons (the heavy, positive parts of atoms) at tumors and releases their energy after traveling a specific distance, thereby causing less damage to tissues they pass through. Although research is inconclusive about whether proton therapy reduces sexual complications, one study did find that men aged 60 or younger treated with this modality experienced little sexual dysfunction; in comparison with the findings of other studies cited in the paper, the amount of dysfunction was comparable to that in populations treated with EBRT in general, but better than that in men treated with prostatectomy.

LDR AND HDR Brachytherapy Round Out Options

But other research has suggested limited advantages of proton therapy. A 2012 study comparing IMRT with proton therapy found that the newer therapy was no more effective in getting cancer in check. In addition, experts warn that proton beam therapy is not only more expensive than other forms of radiation (primarily due to costly machinery), but also might not be the best choice to treat prostate cancer because “critical structures, such as the rectum and urethra, will still get radiation no matter how perfect your particle is,” Yu explains.

Men with early stage, slow-growing tumors who would prefer fewer radiation treatments — or even just a single treatment &mdash; might be candidates for traditional brachytherapy, which places radioactive seeds directly, and permanently, into the prostate gland during a short surgical procedure. Radiation is then delivered slowly, for months, at a low-dose rate (LDR); eventually, the seeds lose their radioactivity.

HDR brachytherapy, a newer approach, is administered through temporary catheters, in which a high-activity source is placed for just minutes to deliver HDR radiation.

[Photo by Liza Bishop, VCU Massey Cancer Center]

Experts have placed some caveats on these treatments. Current guidelines from the NCCN recommend that brachytherapy as a standalone treatment be limited to low-risk or intermediate-risk cases. And for now, HDR is usually reserved for cancers that are progressing.

“Only when you need to deliver a big radiobiological punch — like when the disease is aggressive &mdash; do you go with HDR, typically not for early-stage prostate cancer,” says Dorin Todor, director of the brachytherapy program at Virginia Commonwealth University’s Massey Cancer Center in Richmond. “I think this is where brachytherapy combined with EBRT really shines.

These rules of thumb may be changing, though. According to Todor, “There are ongoing clinical trials trying to prove the equivalence between LDR treatments and one large fraction of HDR for early-stage prostate cancer. Both have the advantage of being a ‘one-stop shop,’ but during HDR, radiation is delivered for only 10 to 15 minutes, as opposed to months or years.”

Radiation can also be delivered directly to bone metastases via radiopharmaceuticals — drugs that contain radioactive elements &mdash; in patients with advanced prostate cancer. These drugs are a particularly useful approach when multiple areas of bone are involved. They can shrink painful lesions and improve quality of life with less exposure to normal tissue.

In May 2013, the U.S. Food and Drug Administration approved Xofigo (radium-223) to treat bone metastases, and a study published in July 2013 in 

 showed that those receiving Xofigo had improved median overall survival (14.9 months) compared with those on placebo (11.3 months).

Although there are many radiation treatment options, with the guidelines continuing to evolve, Levy is pleased that he chose HDR brachytherapy for his localized tumor.

“I didn’t want to take any chances,” he says. “Two days of treatment meant that I would likely not have any problems down the road.”

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New advances in radiation treatment enable higher doses with less damage to nearby tissue.

Scanning the Horizon: Advances in Radiation Treatment for Prostate Cancer

For localized disease, guidelines state that both surgery and radiation are acceptable forms of treatment, and men in this category make up a large number of cases. According to data from the Surveillance, Epidemiology, and End Results (SEER) program, localized disease accounts for about 80 percent of the nearly 221,000 new cases projected for 2015 in the United States.

“It’s mostly early-stage cancers in which radiation therapy is competing with surgery,” says Dorin Todor, director of the brachytherapy program at Virginia Commonwealth University’s Massey Cancer Center in Richmond. “Surgery doesn’t make much sense for anything but early-stage prostate cancer, because if more than the prostate is involved, you’ll need some form of systemic approach.”

To help make a sound decision, patients should consider the following factors.

Younger patients can better tolerate the general anesthesia that’s used in the vast majority of surgical cases, but new minimally invasive techniques (such as robot-assisted surgery) have made surgery a broader option, says James B. Yu, assistant professor of therapeutic radiology at Yale University School of Medicine in New Haven, Conn.

 Insurance coverage varies, but external beam radiation therapy of any type might be more expensive than surgery, according to a 2013 study in the British Journal of Urology International. Researchers found that the costs ranged from about $20,000 for a robot-assisted prostatectomy for low-risk cancer to approximately $50,000 for combined radiation therapy for high-risk cancer. Brachytherapy, however, may be cheaper than surgery. Patients should always discuss the cost of treatment with their health care providers.

 Any side effects from surgery — even the nerve-sparing type &mdash; tend to show up immediately, whereas radiation takes time to produce some of the same changes, experts say. (Which side effects occur and their frequencies vary from patient to patient, regardless of the choice.) For example, about half the men who had normal erections prior to EBRT became impotent within five years, and about one-third of the men who received brachytherapy experienced incontinence.

“We’ve made great strides over the past couple of decades, and prostate cancer remains a very curable disease for the most part,” Yu says. “That’s why we’re focusing so much on side effects and cost. In a way, focusing on these subtle questions is a good problem to have, since so many of these men go on to live such good, long lives.”

Whether to opt for surgery or radiation to treat localized prostate cancer depends mainly on the stage and grade of disease.

Surgery or Radiation for Prostate Cancer: What Determines the Choice?

In 2010, researchers estimated there were more than 1.5 million cancer survivors in the United States parenting children under age 18, so when Christine Egan was diagnosed with stage 2 breast cancer in 2011, she was well aware that hers wasn’t the only family with young children dealing with a cancer diagnosis. But the Bayport, N.Y. mom wanted to make sure her three children—who were 9, 11 and 13 years old when she was diagnosed&mdash;also understood they were far from alone.

Egan enlisted her kids’ help in creating a series of sticky notes with handwritten inspirational messages that she affixed to the dressing room mirror where she underwent 33 radiation treatments. With phrases such as, “Don’t look back—you’re not going that way,” and “Every day may not be great, but there’s something great in every day,” the gesture was designed to boost the spirits of fellow patients. Egan hoped it would also offer her own kids a valuable coping mechanism during a trying time.

“This showed them that this experience was way bigger than just us and made them understand how we can impact someone else,” Egan says.

Honesty, consistency and creativity are vital for children in adjusting to a parent’s cancer survivorship, experts say. Several tried-and-true tactics include:

 Parents should call cancer by its name and tell children what they’re doing to treat the illness, as well as expected side effects. They should make sure kids understand they did not cause their parent’s cancer and that it’s not contagious, says Meredith Cooper, executive director and co-founder of Wonders & Worries, an Austin, Texas-based nonprofit that supports children through parental illness.

 “Children thrive when they know their world is predictable,” Cooper says, adding that they need reassurance they’ll be cared for no matter what. “Keeping routines as normal as possible enhances their sense of security. Likewise, when the routine needs to change—either expectedly or unexpectedly&mdash; having the child know the new plan is very important.”

 Kids can draw pictures, keep journals or even make bracelets with bead colors representing their different emotions about a loved one. “We find expressive art activities one of the best ways to help children express their feelings,” says Sue Heiney, co-director of the Cancer Survivorship Center at the University of South Carolina College of Nursing in Columbia, S.C.

One parent should try to spend at least 15 minutes each day focusing solely on each child in the family, Heiney says. “Talk to them about school, read a book . . . you don’t need huge amounts of time,” she adds. “Just some quality time so the child knows ‘My mother or father hasn’t forgotten me.’”

Consistency, truthfulness and age-appropriate conversations are vital for children in adjusting to a parent's cancer survivorship.

Helping Kids Cope Requires Honesty, Creativity

A few minutes after learning she had breast cancer in 2011, Christine Egan marched up to the makeshift third-floor classroom where she and her husband home-school their children, to share the news. While she didn’t yet know all the details of her stage 2 diagnosis—for which she later underwent a lumpectomy, chemotherapy and radiation&mdash;she did realize that she wanted to be honest about the entire process with her children, who were ages 13, 11 and 9 at the time.

“This was something so tremendous there was no way I could hide it from my kids,” says Egan, a 46-year-old certified health coach from Bayport, N.Y., who’s now cancer-free.

From the start, Christine Egan (second from right) was open about her breast cancer diagnosis with her family: husband Frank (center) and children Emily, Jack and Frank III (from left to right). Photo by Owen Kassimir.

As stunning as a cancer diagnosis may be for an individual, cancer is ultimately a family affair for the 14 percent of survivors who, like Egan, are living with children under 18 years old, according to National Cancer Institute estimates. These youngsters need their own form of healing from the emotional strain of a serious diagnosis, uncertainty about its course, and upended family routines. And just as issues remain for patients moving into survivorship, so too do they remain for their children.

Research indicates that children of all ages may face challenges adjusting to a cancer diagnosis, and an August 2014 study in the journal 

by Birgit Möller and colleagues noted that children of cancer patients are especially vulnerable to developing emotional and behavioral problems because of the disruption to the family that cancer brings. As a result, the study recommended identifying families most in need of psychosocial support and providing not only family-oriented services, but also child-centered services, focusing on family dysfunction to prevent mental health problems in the children.

“I think it’s important children are told as much as they can handle,” says Lynnette Wilhardt, a licensed clinical social worker and director of clinical services for Kids Konnected, a nonprofit organization based in Laguna Hills, Calif., that offers counseling, camps and other support to children whose parents have cancer. “I equate it to the ‘sex talk’—they’ll walk away when they’ve had enough.”

After addressing their immediate worries about how sick mom or dad (or aunt, grandparent or other family member raising them) is, and how the illness will affect their own lives, most children need regular assurances throughout treatment that everything medically possible is being done to deal with the malignancy, says Sue Heiney, a professor of nursing and co-director of the Cancer Survivorship Center at the University of South Carolina College of Nursing in Columbia, S.C. This information needs to be repeated as kids get older, if only because children can absorb more— possibly triggering heightened worries&mdash;as months and years pass.

[Carrie Corey: Parenting with Advanced Cancer]

Cancer in Our Family: Helping Children Cope with a Parent’s Illness

, published in 2013 by the American Cancer Society, the normal spectrum of kids’ possible reactions depends on their ages, but can include resisting naps and bedtimes, clinginess, inattentiveness and arguing more with siblings. More serious reactions that may require professional help, she says, include nightmares, bedwetting, lower grades in school and talking back to parents. A parent’s illness may present unique challenges for older children, including preteens and teenagers, whose worlds are broadening and who consider peers increasingly important. Teens may be resentful, angry and confused about changes in their family life but unable to express their feelings as they test out adult emotions and responsibilities.

With a record 14.5 million cancer survivors in the United States today—almost two-thirds of whom, according to the American Cancer Society, received their diagnosis more than five years ago&mdash;chances are good that most children know someone who has had the disease. But when cancer hits home, even the awareness that it’s increasingly beatable doesn’t inoculate kids from significant psychological effects.

Just as many cancer survivors discover that the end of treatment doesn’t spell the end of cancer’s impact on their lives, so too do their children. Finding a “new normal” can be challenging for all family members, especially for kids old enough to understand that sometimes cancer comes back.

Tailoring information to children’s ages—from simple to more complex, but always honest&mdash;remains the goal as a parent transitions from patient in treatment to survivor, Heiney says.

“Ideally, the cancer experience would be integrated into family life and would be a topic of discussion at various times, including (follow-up) surveillance such as a mammogram or colonoscopy,” she says. “The parent needs to avoid the cancer diagnosis being a family secret, but during survivorship it does not need to be a focus of life.”

Egan uses psychotherapy to manage her own fears of recurrence, an approach akin to parents donning their own oxygen masks on a plane before attending to their children. “If parents are OK, the kids are OK—that’s what we usually say,” explains Heiney, who agrees with other experts that counseling for children&mdash;which can include individual or family therapy&mdash;can be helpful, but isn’t a must unless they’re exhibiting unusual anxiety or other behavioral problems. On the other hand, support groups for children can help normalize the experience and decrease isolation the child may feel, she says. These groups are not intended as therapy, but to help the child cope.

"Tailoring information to children’s ages—from simple to more complex, but always honest&mdash;remains the goal as a parent transitions from patient in treatment to survivor." 

As Heiney recommends, Egan uses her periodic follow-up tests as a springboard for ongoing conversations with her children about her health. But she says they haven’t seemed anxious about what survivorship means or what the future may hold.

“They know cancer can come back, since people are always coming to me for advice when they’re diagnosed,” Egan says. “I think they buy into my message...that cancer sucks, but how can you deal with it? They don’t ask about recurrence... they see that I work on my health every single day.” Heiney contends that most children aren’t as worried about an eventual return of the cancer as they were initially about their parent dying. Still, bringing these fears to the surface instead of bottling them up is a skill like any other that parents can teach and nurture, she says.

Another way to broach survivorship is by participating as a family in an awareness event, such as National Cancer Survivors Day, where the parent’s story can be told, Heiney says.

“I would really impress that this is an opportunity for a family,” says Wilhardt, director of clinical services for Kids Konnected. “Embrace the fact that the whole family is going through this. Our instinct is to protect our kids, but we have to trust that they can handle this and, more importantly, they need to be given the respect to go through this with us.”

During treatment, family roles often realign as members assume new domestic or financial responsibilities to alleviate stress on the ill parent. Teens in particular may end up nursing the parent with cancer, “parenting” younger siblings, or taking on tasks such as house maintenance or meal prep—a shift that can provoke anger at cancer’s impact on their growing-up years. “If teens in the family are given additional responsibilities, we advocate trying to balance that with giving them additional privileges,” says Meredith Cooper, executive director and co-founder of Wonders & Worries, a nonprofit organization based in Austin, Texas, that supports children through serious parental illness. “So if they’re responsible for picking up siblings after school, for instance, maybe their curfew can be extended. This validates to them that they’re meeting those responsibilities well.”

But new burdens, both physical and psychological, can prove crushing in families already in crisis before cancer strikes, whether from divorce, addiction, abuse or financial strain. Numerous studies, including the one by Möller and co-authors that appeared in 

in August, have found that general family dysfunction is the strongest predictor of emotional and behavioral problems in children whose parents have cancer, not the cancer diagnosis itself.

> Children should be told about a parent’s cancer and given regular assurances that everything medically possible is being done to treat it.

> A parent’s cancer can mean a reshuffling of familial roles, which will require some emotional adjustment for both adults and children.

When a parent has cancer, survivorship becomes a family affair.

Helping Children Heal 

Before Matt Ellefson’s non-small cell lung cancer was tested for a biomarker that allowed a single drug to keep it under control, the 51-year-old South Dakota resident underwent standard chemotherapy and radiation treatments that came with typical side effects.

Worst among them were pain from radiation burns near his esophagus and two incidences of radiation-induced pneumonitis (a lung inflammation) that required lengthy hospitalizations.

But in the two years Ellefson has taken Xalkori (crizotinib), a targeted drug inhibiting a cancer-fueling protein expressed by his ALK gene mutation, he has dealt with only one noteworthy side effect—low testosterone levels affecting his energy, which he alleviates with a topical testosterone cream.

In addition to improving the effectiveness of cancer treatments, biomarkers have the potential to help patients avoid burdensome side effects and save money on costly therapies to which a cancer won’t respond. In the journal 

, experts suggest that biomarker use could lower the overall cost of cancer care in the U.S., where health care accounts for nearly onefifth of the gross domestic product.

Without the benefit of biomarker tests for cancer patients, “we tend to overtreat rather than undertreat,” says Daniel Hayes, a professor of medicine and breast cancer research at the University of Michigan in Ann Arbor. “A really good biomarker test is good for the patient and the insurance company. In theory, that’s going to save lots of patients lots of toxicity and lots of third-party payers lots of money.”

But, Hayes adds, for a biomarker test to be valuable, doctors must have “tremendous confidence” in its analytical validity and clinical utility. “It must be shown with high levels of evidence that using the test improves the patient’s outcome.”

Science could help determine the best treatment for individual patients.Ã‚Â 


Biomarkers Could Help Lower Treatment Costs, Side Effects

	When Matt Ellefson received a diagnosis of advanced lung cancer on the last day of 2009, he quickly joined a clinical trial combining standard chemotherapy and radiation treatments with an investigational drug that managed to send his cancer into remission within six months.

	By the time the South Dakota engineer experienced a recurrence 12 months later, an entirely new treatment option had become available. Based on an analysis of Ellefson’s new tumor, removed from a lymph node in his neck, doctors discovered a mutation in a gene called anaplastic lymphoma kinase, or ALK, which occurs in about 5 percent of lung cancers. In 2011, the Food and Drug Administration (FDA) approved a targeted drug, Xalkori (crizotinib), to tackle ALK-fueled lung cancers by blocking a protein produced by the gene. Ellefson now takes two Xalkori pills daily and, at age 51, is cancer-free.

	"This provides so much hope,” says Ellefson, a lifelong nonsmoker. “It was amazing how well the drug worked. I started taking it at the end of October, and by mid-November I was training for a half-marathon.”

	He developed a small brain metastasis in late 2012—not unexpected since Xalkori can’t cross the blood-brain barrier&mdash;that was soon eradicated with stereotactic radiation therapy. “I could noticeably tell I was getting my strength back,” he says of Xalkori’s effectiveness. “I had more energy, and I was more positive.”

	Ellefson's experience demonstrates how biomarkers are transforming cancer care, enabling doctors to personalize their approach to diagnosing and managing the disease. Cancer biomarkers include identifiable gene mutations, proteins, growth factors and other biomolecules that can help diagnose malignancies at earlier stages, classify tumors to determine ideal therapies or monitor patients' treatment responses. Essentially, identifying the right biomarker could affect the entire continuum of cancer care for patients.

Promising Advances, Yet Obstacles Persist

	While hundreds of potential biomarkers have been studied over the past decade—coinciding with quicker, cheaper next-generation gene sequencing abilities&mdash;fewer than two dozen cancer biomarkers are currently FDA-approved, and less than half of those are protein biomarkers detectable in blood. Researchers widely consider minimal or noninvasive biomarker tests, such as simple blood tests, to be the holy grail of the field.

	“Ultimately, the goal we’ve all been working toward is trying to understand the way each tumor is physically built and how they develop in each person,” explains Kenna Mills Shaw, executive director of the Institute for Personalized Cancer Therapy at the MD Anderson Cancer Center in Houston. “We want to deconstruct the actual problem. That’s where biomarkers offer a specific target—and downstream, a specific treatment. If we can understand all the instructions tumors use, we can go after their specific vulnerabilities, their Achilles’ heels.”

	But biomarker research is complex. Understanding the molecular alterations that characterize cancer cells requires a combination of genomics (analyzing DNA), proteomics (studying proteins) and transcriptomics (assessing RNA molecules, which translate the DNA code into proteins). And the research process involves three essential steps: discovery, verification and validation.

	Discovering potentially important biomarkers isn't a problem. Groups such as The Cancer Genome Atlas (TCGA), a consortium launched in 2006 to use DNA sequencing to identify the most common and significant mutations in cancers, recently learned that 127 genes were significantly mutated among 12 different types of cancers, including breast, colon, lung and ovarian malignancies as well as acute myeloid leukemia. Endeavors such as this have produced biomarker breakthroughs that already affect treatment for millions of people with cancer, including the discovery of BRAF mutations in metastatic melanoma. HER2 mutations in some breast and gastric cancers, and several serum marker proteins that can signal recurrence and help determine prognosis in ovarian cancer. 

[Biomarkers Could Help Lower Treatment Costs and Side Effects]

	In the hands of groups such as TCGA, next-generation gene sequencing is fueling much of the biomarker revolution, says Daniel Hayes, a professor of medicine and breast cancer research at the University of Michigan in Ann Arbor. Between 300 and 350 important abnormalities are expressed in humans’ 15,000 or so genes, he notes.

	“The wave of the future is doing complete transomics of tumors—next-generation sequencing that either sequences the entire genome or the part that encodes for expressed genes,” Hayes says. “The brave new world right now is that we really don’t know what to do with these kinds of massive analyses . . . because we’re not talking about a single test. That gets complicated, too.”

	And expensive. At the center of this information glut is the burgeoning field of bioinformatics, which develops methods for storing, retrieving, organizing and analyzing biological data to support the identification of trends and patterns that prompt new therapies. But while the costs of sequencing personal genomes has plummeted to a few thousand dollars, the downstream expenses associated with tracking and mining this compiled data are seldom considered, says Mark Gerstein, co-director of the Yale Computational Biology and Bioinformatics Program in New Haven, Conn.

	Gerstein co-authored a 2011 paper published in the journal 

 explaining how the real costs of sequencing are higher than thought, creating a gate-keeping effect for scientists hoping to explore potential biomarkers.

	“Sequencing the genome of a person who has cancer—even multiple times&mdash;is quite reasonable because the cost has come down so much,” Gerstein says. “But the bottleneck now is the interpretation of all the sequencing and coming up with a way to understand all this data in simple terms. We don’t really have that yet.”

	With so much focus on research, why are so few biomarkers considered reliable? Scientists say a serious breakdown in the research process—fueled by a lack of money, time and technology&mdash;hits the pause button on crucial clinical trials that might offer cancer patients wider and better drug options.

	Moreover, current technologies can’t consistently verify the presence of candidate biomarkers in patient samples, says Ross Molinaro, an assistant professor of pathology and laboratory medicine at Emory University School of Medicine in Atlanta. “Verifying and validating biomarkers may take years to achieve, especially in cases where disease prevalence is low and the ability to collect samples from these patients is limited.”

	Sometimes, stored tissue from prior clinical trials can be used in biomarker research, offsetting cost and availability obstacles, but these samples aren’t always ideal because the cells could have changed due to freezing or from the effects of earlier cancer drugs, researchers say.

	Hayes contends that many more biomarkers would be considered clinically useful if pharmaceutical companies and government agencies invested as much in biomarker research as in drug development.

	“In general, tumor biomarkers have sort of been the funny cousin in the corner, compared to drugs and therapeutics,” says Hayes, who helped establish guidelines for the development and validation of biomarkers. “It’s hard to make evidence-based guidelines because we don’t have the evidence.”

	Cancer itself is also to blame for the dearth of reliable biomarkers, since even within single tumors, gene mutations may differ from cell to cell. That means a targeted treatment aimed at one biomarker-identified mutation may miss the mark with another, allowing the malignancy to proliferate.

	Shaw explains that tumors often evade some treatments because, as cancer cells spread, they send out error messages to new cells, essentially ensuring that not all tumor cells will be identical. “When we ‘kill off’ part of the tumors that might have a given biomarker profile, that doesn’t mean the residual tumor cells or recurrences are necessarily the same genomically,” she says.

	On the flip side, however, researchers from TCGA and other projects have found that some tumor types that weren’t considered similar share an underlying genetic likeness, unexpectedly opening the possibility of treating them with the same drugs. For example, nearly 70 percent of head and neck squamous cell carcinomas appear to have the same mutant p53 gene found in 95 percent of ovarian cancers.

	Because tests looking for a single biomarker may not be sensitive or specific enough to both distinguish normal from diseased samples and tease out cancers from other conditions—important for preventing falsepositive and false-negative results&mdash;clusters of cancer biomarkers are beginning to be evaluated in single tests. One such test already available, OVA1, measures five biomarkers to determine the likelihood that an ovarian mass is cancerous before surgery.

	But finding the "right" patients for testing new biomarkers in clinical trials can also be elusive, Shaw notes, especially as tests for multiple biomarkers begin to proliferate.

	“We can intellectually design those experiments, but finding a big enough sample size to test is where it becomes difficult,” she says. “Add five biomarkers to one test for breast cancer, for example, and you’d have a much smaller population with that specific disease. We’d potentially have a very sensitive biomarker signal that’s testable, but a very small set of patients to actually work with.”

Biomarker Workhorses Spawn New Treatments

	By tapping into an existing or readily identifiable patient pool, scientists are using some well-established biomarkers to produce more effective treatments for patients whose first-line therapies have failed. Consider patients whose breast tumors overexpress the protein HER2, which is found in about 20 percent of invasive breast cancer cases. This easily identifiable biomarker offers a fixed target for a steadily expanding array of therapies.

	Jennifer Schreck’s life was transformed by the latest of four approved HER2-targeted drugs. After receiving a diagnosis of advanced breast cancer in 2006 at age 33, her condition worsened while on standard taxane-based chemotherapies combined with Herceptin (trastuzumab), the first anti-HER2 drug, which was approved in 1998.

	Schreck, now 42, had to use a wheelchair by 2010—with the cancer in her liver and lungs as well as most of her bones&mdash;when she entered a clinical trial for Kadcyla (ado-trastuzumab emtansine, also known as T-DM1). The therapy links Herceptin with a potent tumor-killing drug to destroy only HER2-positive cancer cells, minimizing side effects to healthy cells. Schreck received Kadcyla every three weeks as a 30-minute infusion.

	Kadcyla was Schreck’s ticket back to camping, hiking, biking and the active lifestyle her family enjoys, which metastatic disease had initially forced her to abandon.

	“After the second treatment, there was dramatic improvement,” says the Aurora, Ohio, resident. “I felt like a windup doll—I was walking and not in pain. My life is so much better.”

	While Schreck’s cancer has diminished and even disappeared in spots, she’s under no illusion that the biomarker-driven treatment will be a cure. Still, Kadcyla—shown to extend survival by up to five months on average compared with alternatives&mdash;gave her time with her husband and two young sons she might not have had, and she experienced only minor side effects, including constipation and low platelet counts.

	“For whatever reason, I’m still responding and I’m very thankful,” she says. “I’m not just existing, I’m living.”

	Aiming for similar successes, scientists remain hopeful about the potential of increasingly translating biomarker science into patient care. But they are also realistic about its inherent problems.

	“Any time there’s a goal to combine multiple sets of inherently complex information, challenges may arise,” Molinaro says. “I compare this to doing your taxes. In some cases, a tax accountant can be used to simplify the complex process. In the biomarker pipeline, a universally accepted ‘biomarker accountant’ has yet to be identified.”

	> Patients should ask if a biomarker could help determine the ideal therapy. 

	> Some biomarkers can also reveal treatments that won't be effective.

The personalized medicine revolution is gaining momentum.

Personalizing Cancer Care with Precision Medicine

Whether to opt for surgery or radiation to treat localized prostate cancer depends mainly on the stage and grade of disease. But localized prostate cancer accounts for about 80 percent of the nearly 240,000 cases diagnosed each year in the U.S., according to the National Cancer Institute, and guidelines state that both surgery and radiation are acceptable forms of treatment.

“It’s mostly early-stage cancers in which radiation therapy is competing with surgery,” says Dorin Todor, director of the brachytherapy program at Virginia Commonwealth University’s Massey Cancer Center in Richmond, Va. “Surgery doesn’t make sense for anything but early-stage prostate cancer because if more than the prostate is involved, you’ll need some form of systemic approach.” What should be considered?

AGE: Younger patients can better tolerate the general anesthesia that’s used in the vast majority of surgical cases, but new minimally invasive techniques (such as robot-assisted surgery) have made surgery a broader option, says James B. Yu, assistant professor of therapeutic radiology at Yale University School of Medicine in New Haven, Conn.

COST: Insurance coverage varies, but radiation therapy of any type might be more expensive than surgery, according to a 2013 study in the British Journal of Urology International. Researchers found the costs ranged from about $20,000 for a robot-assisted prostatectomy for low-risk cancer to approximately $50,000 for combined radiation therapy for high-risk cancer.

SIDE EFFECTS: Any side effects from surgery—even the nerve-sparing type&mdash;tend to show up immediately, whereas radiation takes time to produce some of the same changes, experts say. (Which side effects occur and their frequencies vary from patient to patient, regardless of the choice.) For example, about half of men who had normal erections prior to external beam radiation treatment became impotent within five years, and about a third of men who received brachytherapy experienced incontinence.  “We’ve made great strides over the past couple of decades, and prostate cancer remains a very curable disease for the most part,” Yu says. “That’s why we’re focusing so much on side effects and cost. In a way, focusing on these subtle questions is a good problem to have since so many of these men go on to live such good, long lives.”

Whether to opt for surgery or radiation to treat localized prostate cancer depends mainly on the stage and grade of disease, but both therapies are acceptable forms of treatment.

Decision Time: Surgery or Radiation for Early-Stage Prostate Cancer

Michael Fisch’s patient seemed devastated to learn that her breast cancer had recurred—but not for the reasons he thought.

“Her reaction wasn’t about her survival or her prognosis but about what it meant to her hair,” recalls the chairman of the department of general oncology at MD Anderson Cancer Center in Houston. “When she had previously lost her hair due to treatment, her daughter would duck down in the car, so friends wouldn’t see her. This wasn’t about hair loss; it was about something much more profound.”

For many patients, anxiety about chemotherapy side effects, such as pain, fatigue or hair loss, can be worse than the side effects themselves. A 2008 survey by the National Coalition for Cancer Survivorship and Sanofi-Aventis highlighted this fact, indicating that 76 percent of people with cancer were most fearful of potential chemotherapy side effects. Of the 91 percent who experienced them, however, 87 percent said the effects were more manageable because of supportive care products.

[Read more about overcoming fear of side effects in "Never Fear"]

How can patients best contend with these worries? Clear and frequent interactions between doctors and patients are crucial, according to Dawn Hershman, an associate professor of medicine and epidemiology at Herbert Irving Comprehensive Cancer Center at Columbia University in New York.

“The best thing is to communicate with your physician,” Hershman advises. “Some side effects can be prevented, and not everyone gets every side effect. Often patients’ concerns are disproportionate to what they’ve experienced, and usually a lot of it can be managed.”

Doctors can also do more to ask patients the right questions about their concerns, Fisch notes. “They can say, ‘Tell me more about what you’re scared about,’” he says. “Usually, missed opportunities are unspoken or unassessed. Symptom management is an assessment game—tricky but gratifying.”

Anxiety about potential side effects is common, and can usually be alleviated by a talk with your physician.

Anxious About Side Effects?

Once Shirley Billigmeier got past the initial shock of receiving a breast cancer diagnosis in 2009, at age 59, she began researching all she could about treatment options. Her stage 1 cancer was caught early, but an aggressive cell type meant Billigmeier’s lumpectomy would need to be followed by chemotherapy to lower her chance of recurrence.

Learning that one of her chemotherapy drugs, docetaxel, would almost certainly cause hair loss, Billigmeier’s heart sank. She ordered a wig but kept on researching—learning from her dermatologist that a cold cap might stop her from shedding her locks. Using cold caps requires careful coordination during chemotherapy treatments, and because they are not yet approved by the Food and Drug Administration, many medical professionals are skeptical of their promise.

“I had to keep them on dry ice since the cap has to be minus 30 degrees Celsius,” explains Billigmeier, now 63 and cancer-free. “But I said, ‘I’m going to do this. I don’t have to lose my hair.’ In my mind, I had no doubts it would work.”

Hair loss is only one of many potential downsides of chemotherapy, which is increasingly effective in many malignancies but also associated with short- and long-term side effects, including fatigue, nausea, low blood cell counts and potential nerve injury. But patients have options to counter certain side effects of chemotherapy.

The goal of chemotherapy is to destroy cancer cells. But the way it works—by killing rapidly growing and dividing cells&mdash;is why it causes unwanted side effects. As it attacks those fast-growing cancer cells, it also kills off quickly growing healthy cells in areas, such as in hair roots, bone marrow, and cells lining the mouth, esophagus, stomach and intestines. This causes well-known issues, including hair loss, nausea, vomiting, fatigue, low blood cell counts and mouth sores.

And while certain medications produce particular side effects (for instance, platinum- and taxane-based chemotherapies can trigger nerve damage), determining who will suffer specific effects and for how long is an inexact science.

“What people don’t always realize is they’re not necessarily going to immediately feel better when they’re done with treatment,” says Dawn Hershman, an associate professor of medicine and epidemiology at Herbert Irving Comprehensive Cancer Center at Columbia University in New York. “And that results in a lot of psychological distress.”

What people don’t always realize is they’re not necessarily going to immediately feel better when they’re done with treatment. And that results in a lot of psychological distress.

But doctors can often make a well-informed guess about who might be more at risk for specific chemotherapy side effects, says Michael Fisch, chairman of the department of general oncology at MD Anderson Cancer Center in Houston. Comparing patients to hikers approaching the edge of a side-effect cliff, he says “different patients are closer to the edge to start with,” and whether a patient ends up experiencing a chemotherapy side effect “is very complicated.”

“If you already have diabetes, for example, it won’t take much of a nudge to cross the line to peripheral neuropathy,” he says of the nerve damage that results in pain and tingling and is a pre-existing condition in many older people with diabetes. “People with more cardiac risk factors may be more at risk for cardiac toxicity from certain types of chemotherapy.”

Fisch explains that the degree to which an individual experiences some side effects will depend not only on the nature of the person but on the nature of the drug.  “In other words, it depends on how strong the nudge is and how resilient you are to the nudge and also how close you are to the side-effect cliff.”

People with more cardiac risk factors may be more at risk for cardiac toxicity from certain types of chemotherapy.

Some side effects of chemotherapy, such as nausea and vomiting, are readily preventable thanks to drug advancements. As cancer treatments improve in effectiveness, so, too, do medications and techniques to prevent or minimize some of the most-feared chemotherapy side effects.

So what can patients do to prevent certain side effects of chemotherapy? Some preventive methods are backed by dozens of research studies, while experts caution that others are more hit-or-miss and untested.

[Blog: Did integrative therapy approaches help you in dealing with side effects from cancer or treatment?]

 As many as 40 percent of patients receiving chemotherapy experience mouth sores or oral mucositis, according to Cancer.Net. But these painful sores, which can extend down the throat, are not only a nuisance—they can deter patients from eating and drinking, thereby affecting nutrition and energy levels.

But a simple measure might prevent mouth sores in some patients. A 2012 study in Iran of 80 patients indicated that those who placed ice or ice-cold water in their mouths from five minutes before starting to five minutes after completing a chemotherapy treatment had a 32.5 percent lower incidence of oral mucositis than those who had nothing in their mouths. The intense cold is thought to temporarily narrow blood vessels in the mouth, a process called vasoconstriction, which diminishes blood supply, thereby reducing chemotherapy exposure for these cells. Additional research is needed, however.

Cold caps for hair loss and cold gloves for nail loss:

 Using the same tenets of vasoconstriction, deeply cooling the scalp or hands during chemotherapy can ward off hair or nail loss by temporarily hindering blood flow to those areas. While both methods are still being researched in the U.S., several European studies have shown some benefits.

Billigmeier’s success with cold caps prompted her to co-found a nonprofit, The Rapunzel Project, to create awareness about cold caps and to help supply the specialized freezers they require to medical facilities. “Whether other patients use the cold caps or not isn’t the issue,” she says. “We just wanted to make sure they were aware that [the cold cap] existed and could choose it or not.”

A 2005 review of 53 studies on scalp cooling, published in the 

, for example, showed that the success rates of patients keeping their hair varied greatly, but “cooling time, the chemotherapy used and the temperature seem to be influential,” according to the authors.

While less prevalent than chemotherapy-associated hair loss, nail changes were the focus of a 2005 study that tested a so-called frozen glove on patients receiving docetaxel. Participants wore the glove on one hand and nothing on the other. According to the findings, 89 percent of the gloved hands had no nail toxicities compared with 49 percent in the non-gloved hands.

Cymbalta (duloxetine) or glutamine for neuropathy:

 One of the most difficult chemotherapy side effects is peripheral neuropathy, a form of nerve damage that can range from mild to severe—from tingling in the hands and feet to electric shock-like pain. Such effects can hinder balance and activities of daily living, such as buttoning a shirt. Neuropathy is usually temporary but can be long-lasting in some patients.  In a phase 3 clinical trial published this year in the 

Journal of the American Medical Association

, patients who took the antidepressant Cymbalta (duloxetine) reported a decrease in any amount of neuropathic pain compared with those given a placebo—59 percent versus 38 percent.

Meanwhile, the amino acid glutamine has variably been shown to provide a protective effect on nerves. A small 2005 study of 46 patients treated with paclitaxel showed that those who took glutamine developed significantly less weakness, loss of “vibratory sensation” and toe numbness than those who did not take glutamine, but larger studies are needed to confirm this.

 Neutropenia, extremely low levels of neutrophils (a certain type of white blood cell), is a common result of most chemotherapy regimens. But plunging blood cell counts and the duration of this low point—which invite life-threatening infections&mdash;can be as dangerous as cancer itself.  Fever, which can sometimes be the only sign of infection, along with low neutrophil counts, is called febrile neutropenia.

Blood-forming molecules called granulocyte-colony stimulating factors (G-CSFs) can stimulate white blood cell proliferation, despite chemotherapy’s toxic effects. In a 2007 review of published randomized trials printed in the 

, researchers reported a 46 percent lower relative risk of febrile neutropenia in patients receiving G-CSFs compared with control patients.

Additionally, cutting the risk of neutropenia also lowers the chances of chemotherapy dose reductions or delays. In the past, patients required daily injections of a growth factor for several days after each dose of chemotherapy, but a long-acting preparation is now also available for use as a single injection per cycle of certain chemotherapy regimens.

Certain side effects of chemotherapy can be prevented.

Crisis Control: Preventing Side Effects Effectively

An array of medical professionals are likely to be part of a patient’s healthcare team. Here’s a rundown of the roster:

 treat cancer with chemotherapy, biologic therapies or other types of cancer-fighting drugs, and sometimes specialize in one or more specific malignancies.

 use surgical procedures to remove tumors or portions of tumors, and often specialize in surgery at one region, such as the brain or spinal cord, or organ system, such as the digestive organs.

 use radiation therapies to treat cancer. They determine the dose, schedule and type of radiation necessary, and manage physicists and radiation technologists who calculate the doses and fields, and who operate radiation equipment.

 specialize in treating cancers in children and teens, sometimes in patients up to age 20.

 diagnose and treat cancers of women’s reproductive organs and are usually trained in surgery and chemotherapy administration.

 diagnose cancers using imaging tests, such as mammograms, ultrasounds, X-rays, MRI scans, CT scans and PET scans.

 use imaging scans, such as ultrasound, CT and MRI, to obtain biopsies or to guide treatment delivery directly to tumors, including those that use heat, cold or radioactive beads to kill malignant cells or hinder blood supply to a tumor.

 classify different types of cancer by studying cells and tissues under a microscope and use special tests to study proteins and genes on cells. Their diagnosis typically plays a large role in the choice of treatment(s) pursued.

 perform operations for many reasons, not strictly to treat cancer.

 provide handson care for patients and may see them independent of doctors.

A host of other medical professionals collaborate with physicians and other major figures on the healthcare team, including:

help guide patients and families through the treatment process.

dispense oral anticancer treatments and medications to reduce treatment side effects and are involved in patient education.

conduct some tests, prescribe medications and perform certain procedures.

help manage the nutritional aspects related to cancer care.

provide counseling, advocacy and referrals for financial, spiritual and mental health needs.

An array of medical professionals are likely to be part of a patient's healthcare team.