Mike King

Cancer patients should be on the lookout for these specific infections that can complicate treatment:

. There are more than 30 different types of 

. They are common in patients with chronic diseases, including diabetes and cancer, and most often start on the skin. Some staph infections can be caused by food poisoning. Most can be treated with antibiotics.

 One of the most dangerous of these is methicillin-resistant 

, known as MRSA. These infections, almost always acquired in a healthcare setting, are much more stubborn to treat and can be life threatening.

 A type of yeast infection on the skin and mucous membranes, 

 can sometimes occur with the use of antibiotics or as a result of a weakening of the immune system from having cancer itself or radiation and/or chemo. Generally they can be treated with antifungal agents.

A yeast-like fungal infection that settles in the lungs, sometimes as the result of immunotherapy connected to bone marrow transplants, 

 can be treated with antibiotics and, depending on the severity of damage to the lungs, corticosteroids.

 This bacterial infection can be especially problematic, playing havoc with the colon and digestive tract. It is often passed on in healthcare settings, especially to patients who have been on antibiotics and altered their normal colonic bacteria or who are hospitalized long term and are already immunosuppressed. A minimum 10-day antibiotic regimen is usually required for serious cases.

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Cancer patients should be aware of the risk of infections.

Risky Infections

When Chris Prestano learned in 2008 that she had thyroid cancer, she decided to commute between her home in New York City and Baltimore so that experts at Johns Hopkins Hospital could treat her.

Because she also has type 2 diabetes, which can lead to skin infections, Prestano knew that even a relatively simple surgery like removing her thyroid posed a risk. She and her physicians took every precaution necessary, including pre- and postoperative antibiotics, but it didn’t stop her from developing an infection. Now, more than two years later, she is battling a surgical wound infection that aggravates her recovery from cancer as well as her diabetes.

“My team of doctors is the best team I think I could assemble,” Prestano says. “We were very careful, very cautious going into this, and it still happened.”

Most cancer patients are aware of the tradeoff: Targeting cancer cells with chemotherapy agents and radiation or removing damaged organs and tissue through surgery greatly increases the chance of infection by germs that attack weakened immune systems.

The risk-versus-benefit equation is a standard topic whenever options are discussed. And both patients and their healthcare teams are getting savvier about what they can do to control infection risks before, during and after treatment.

Still, since that first thyroid operation, Prestano has been in and out of the hospital several times to treat the surgical-site infections. Among other procedures, she’s received five rounds of steroids, pulsed-dye laser treatments and surgical alterations to the scar. The loss of her thyroid and the recurrent infections has exacerbated her diabetes. Before surgery it was controlled without drugs, but now she is insulin-dependent.

“I had no idea it would take this long to heal,” says Prestano, 30, who moved to Frederick, Md., last year and now makes a much more manageable 50-mile drive to Johns Hopkins every three to five weeks so that doctors can monitor her progress. “I was more concerned about the infection and recovery from the surgery than the cancer itself.”

Prestano says she usually avoids large groups, rarely socializes with anyone who seems to be fighting a respiratory infection and has become vigilant about using hand sanitizers. “That’s the price we pay as cancer patients, I guess,” she says. While most patients won’t have the difficulties that Prestano has, it’s important to know Prestano is not alone.

I was more concerned about the infection and recovery from the surgery than the cancer itself.

Since the skin is the body’s first line of defense against infection, any break in it—through a surgical site or where a central line catheter is inserted into a vein to facilitate chemotherapy infusions&mdash;becomes a potential source for infection. Even subcutaneous central venous access devices, in which medicine is released through chest ports implanted under the skin’s surface, get infected about 5 percent of the time.

One of the most risky complications for any cancer patient is neutropenia, a hematologic disorder characterized by a lack of neutrophils—the granular white blood cells that fight micro-organisms, particularly bacteria.

Even though these treatments carry certain risks, cancer patients and care-givers can take some simple precautions to prevent infection. Wash your hands with warm, soapy water before eating or touching your face, and wash them again after blowing your nose or sneezing. Also, use hand sanitizers or disinfecting wipes after contact with items frequently touched by others, such as ATMs or grocery carts. Patients, caregivers and other family members should get annual influenza vaccines to prevent the virus’ spread. Finally, be aware of the symptoms of infection, such as fatigue, fever, redness and swelling, and contact your healthcare provider if those symptoms persist. 

Healthcare providers in most states have voluntarily started using an infection-control checklist when inserting and working with infusion ports in patients, says Peter Pronovost, MD, professor of anesthesiology and critical care at Johns Hopkins, who has spearheaded the checklist effort. Patients and family members, he adds, should be aware of them too and insist that they be followed. For example, patients should confirm that medical personnel have washed their hands with soap and water or alcohol gel before and after examining the patient, as well as when inserting, replacing, repairing or dressing a catheter; disinfected the patient’s skin before inserting a catheter and during dressing changes; maintained aseptic technique by wearing a mask, sterile gown and sterile gloves—as well as draping the patient with a sterile sheet&mdash;when inserting a catheter.

Each year, an estimated 60,000 cancer patients are hospitalized for chemotherapy-induced neutropenia. A patient dies every two hours from the complication, according to the CDC Foundation, an independent nonprofit organization. The overall mortality of cancer patients hospitalized due to febrile neutropenia, or neutropenia with fever, is estimated between 9.5 and 11 percent, the foundation reports.

While infections in healthcare settings correctly get the most attention, the risk of neutropenia also extends to other widely prescribed anticancer treatments given in a variety of settings.

In February, researchers examining 16 randomized control trials of Avastin (bevacizumab) found that patients prescribed the drug in combination with chemotherapy or biological therapy were at increased risk of death from neutropenia compared with patients who were getting conventional chemotherapy or other biologic treatments. While some cancer patients may still benefit from taking Avastin, they and their oncologists should be aware of the risk of neutropenia and other life-threatening effects, says Daniel F. Hayes, MD, a professor of internal medicine at the University of Michigan Comprehensive Cancer Center in Ann Arbor, who also serves as co-director of the Breast Care Center and clinical director of the breast cancer program.

The CDC Foundation and Amgen, a maker of anti-infective prophylactic drugs, are collaborating on a three-year effort to raise awareness of preventing infections in cancer patients. An Amgen-sponsored survey of cancer patients in 2009 showed that nearly one-fourth experienced an infection within the first year of chemotherapy. Sixty-one percent of those had more than one infection, and all of them took at least a week to recover, often interrupting their chemotherapy regimens.

Experts say cancer patients must know their infection risks as well as preventive steps they can take depending on their cancer type and treatment regimen. 

 The body’s immune function often decreases in the hours immediately following surgery and may take many months to fully recover. Using antibiotics prior to surgery is sometimes recommended for those most prone to infection.

According to the American Cancer Society (ACS), the risks for patients include how long the patient is in the hospital, the extent of the surgery, the length of the operation and the amount of bleeding. Patients who have had previous treatments for cancer, including chemotherapy and radiation, and those who are diabetic or poorly nourished going into the surgery are also at greater risk.

The surgical site itself is the most common place for infection to take hold. In addition to the complications caused by infection, including treatment delays, it can also increase medical costs. A 2008 study of women undergoing breast surgery showed that surgical-site infections raised the cost of care by more than $4,000 compared with women who came out of surgery free of infection, especially women undergoing mastectomies.

 Patients’ immune systems could be impacted by the types and dosages of chemotherapy, frequency of treatment and the cancer type and stage. Age, nutritional status and prior treatments also impact how the body’s infection-fighting ability is affected by chemotherapy.

Patients with central venous access devices should be especially vigilant. Central lines deliver chemo agents and other medications directly into the bloodstream, usually via a catheter placed in the chest, neck or groin. Because the lines stay in for days, sometimes weeks, they must be routinely handled and can become the site for infections. Even medication ports placed under the skin, usually in patients needing long-term infusion, can become infected below the surface. Patients should watch for redness, swelling and drainage from skin around the catheter or above the port site, as well as other symptoms, such as sudden fever or chills. 

 Radiation’s effect on the immune system, much like that of chemo, is exerted through changes to the bone marrow. Unlike chemo, it affects bone marrow only within the treatment field (“inside the beam”), so it has little impact when the fields are small. However, depending on the part of the body radiated and the dosage, it can also increase the risk of skin damage and infection. Patients who undergo total body irradiation should know that it is much more likely to trigger very low white blood cell counts, which can be risky. The ACS recommends patients be aware of their radiation dose, how often it is given and what parts of the body are getting the most radiation when discussing treatment options with their physicians.

 Immunotherapy boosts the immune system to recognize and attack specific cancer cells but sometimes can change the way the immune system works. Some forms of immunotherapy cause the level of all white blood cells to drop, not just neutrophils. When lymphocyte levels become too low, the risk of certain viral and fungal infections increases. But most often the neutrophil counts return to normal soon after treatment is stopped, even though lymphocyte counts stay low for months.

  Bone marrow transplants pose the most significant risk because they often involve very high doses of chemo and total body irradiation, which severely weakens the immune system. That’s why stem cells are removed from the body before treatment or taken from a donor and re-infused after the procedure so that the immune system can be rebuilt. Precautions include keeping patients in an access-controlled environment of the hospital until white blood cell counts reach normal levels—a wait that can often take weeks. During this time, exposure to people outside of the medical team is severely limited, and patients must be monitored for fever and other signs of infection.

Reducing the risk of infection for cancer patients in treatment.

Germ Warfare

For more than a century cancer was defined largely by what a pathologist observed under a microscope. The “gross morphology”—the shape, the structure and the component parts of the cancer cells taken from a biopsy&mdash;provided the only real road map for treatment.

And it wasn’t so long ago that cancer researchers kept most of their records on paper, sharing their findings with fellow researchers by sending tissue samples through the mail and transmitting notes over facsimile machines. Even after the World Wide Web was up and running, clinicians relied heavily on medical journals, scientific meetings and other methods of dissemination of research to make critical decisions about how to help patients with advanced forms of the disease. 

Modern medicine no longer relies on such outdated research protocols.

 (via computer) research, gene mapping and detailed digital pathology, scientists can now peer well beyond the biopsies of patients and predict pathways inside cells that look harmless but may provide the triggering mechanism that unleashes cancer’s spread. This, in turn, can lead to targeted treatments against some of the most difficult and lethal forms of the disease.

The programming infrastructure that enables information and analytical resources to be shared efficiently and securely among cancer researchers is called caGrid. The open-source information network that caGrid supports is called caBIG (Cancer Biomedical Informatics Grid), a major initiative of the National Cancer Institute. These developments have propelled cancer research into the molecular age and hold great promise for future clinical care.

Scientists can now peer well beyond the biopsies of patients and predict pathways inside cells that look harmless but may provide the triggering mechnism that unleashes cancer's spread.

 research is concentrating on the genetic pathology and treatment outcomes of brain tumor patients obtained through the Cancer Genome Atlas and other sources residing on the caBIG.

By utilizing rich, molecular data sets, linking them to digitized pathologic slides and annotated neurological images—as well as detailed information about patient treatments and results&mdash;brain tumor research can be conducted on a much larger scale and at a much deeper level than ever, says Daniel Brat, MD, PhD, a professor of pathology and laboratory medicine at Emory University in Atlanta. (Similar work is going on at other centers studying lung and ovarian tumors&mdash;two other forms of cancer that have proven to be stubbornly resistant to conventional therapy in patients with advanced forms of the disease.)

Patients who agree to participate in the research allow tissue samples, radiographic images, clinical notes and other details of their diagnosis and treatment to be shared with the cooperating institutions, which in turn agree to protect their identities. Names and other information that would personally identify the patient do not become a part of the record.

Researchers at Emory and elsewhere learned in the space of a few months what would have otherwise taken years to find about a range of genetic mutations in some glioblastomas, the most common malignant brain tumors in adults. 

Correlating this information may allow researchers to target specific therapies for specific tumor types to keep them from triggering the genetic “on/off” switch that spreads the cancer so rapidly and leads to death, Brat believes. Similarly, they may find that some forms of therapy cause a hypermutation of the gene and should therefore be avoided in some patients.

Modern medicine no longer relies on information just gleaned from under a microscope.

Mining Cancer Data in the Molecular Age

Over the past two decades, the FDA has changed its drug-approval process several times, with each iteration aimed at speeding the time it takes for medications to go from clinical research to routine use. 

For drugs being developed to treat serious and life-threatening diseases, such as metastatic cancers—those that seem to have a low risk of serious complications and some preliminary evidence of prolonging survival&mdash;the process can be even faster. 

The agency allows these drugs on the market on a conditional basis, but usually demands the manufacturer conduct ongoing, controlled studies to determine whether the preliminary promise holds true. The manufacturer is required to compile these studies for several years after the drug gets preliminary approval. Once confirmatory data is compiled, the drug is eligible for traditional approval from the agency.

Manufacturers can ask that drugs be assigned to one of three approval tracks.

: Moving drugs that fill unmet needs and treat serious conditions, such as cancer and Alzheimer’s, as fast as possible through the pipeline. 

: Determining whether the drugs impact survival, improve day-to-day functioning and prevent the likelihood of the disease progressing if left untreated.Preliminary studies must indicate some advantage over available treatment, an alternative to drugs with more serious side effects, improvement to diagnosing a serious disease where early diagnosis affects  outcome or decreasing the chances of toxicity of an accepted treatment.

: Conditional approval for drugs going through clinical trials that show a significant outcome prior to trial completion. 

: Efficacy must be verified in a phase 3 or 4 trial. Drugs don’t necessarily have to prove they significantly prolong lives. They can be measured on what researchers call a “surrogate endpoint,” which is a clinically meaningful outcome that can be a physical sign or laboratory measurement that is known to correlate with a more standard approvable endpoint. For example, whether patients’ tumors show significant shrinkage.

: Drugs that offer significant improvement to existing therapies or offer treatment where no adequate therapy exists can have a priority review, where the FDA agrees to a hurried-up hearing process and reduces other regulatory hurdles. 

: A drug must show the potential to significantly advance treatment, including substantially reducing a drug reaction or showing effectiveness in a new subpopulation of patients, such as children.

The FDA's drug-approval process has several tracks that help medications quickly go from clinical research to clinical use.

Mike King

Risky Infections

Germ Warfare

Mining Cancer Data in the Molecular Age

A Primer on How Faster Approval Works

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