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July 10, 2012 • Volume 9 / Number 14

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Some Children with Hodgkin Lymphoma May Not Need Radiation Therapy

A radiation therapist preparing a child for radiation therapy

Children with Hodgkin lymphoma who have favorable clinical features and who respond early to chemotherapy may not need treatment with radiation. The finding, reported in the June 27 JAMA, is from a clinical trial of 88 patients with low-risk disease.

Patients who had an early complete response to the chemotherapy regimen used in the trial and were not treated with radiation therapy (as stipulated in the study protocol) had 5-year survival rates similar to those of children who did not have the same response to chemotherapy and therefore required radiation. Read more > >


Dr. Julia H. Rowland

Cancer Survivorship Research: Translating Science to Care

The director of NCI's Office of Cancer Survivorship shares some highlights from the Sixth Biennial Cancer Survivorship Research Conference



Oncology Nursing icon

Special Issue on Oncology Nursing

Don't miss our July 24 special issue, which will highlight the role of nurses in cancer care. Topics will include the role of nurse navigators, the partnership between oncologists and nurses, how nurses support family caregivers, clinical trial ethics and oncology nursing, and compassion fatigue among oncology nurses and how to address it.

Past special issues have focused on obesity and cancer research, adolescent and young adult cancers, and clinical trials enrollment.



  • FDA Update

    • FDA Approves Test to Aid Post-PSA Biopsy Decisions
  • Update

    • Popular NCI Publications Now Available as E-Books
    • NCI Mobile Website Rated among Top 10 Federal Apps
  • Notes

    • Free Workshop for Cancer Survivors: Managing Post-Treatment Neuropathy
    • Funding Available to Support Collaborations between U.S. and Chinese Scientists

Selected articles from past issues of the NCI Cancer Bulletin are available in Spanish.

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Featured Article

Some Children with Hodgkin Lymphoma May Not Need Radiation Therapy

A radiation therapist preparing a child for radiation therapyA recent study in JAMA showed that children with Hodgkin lymphoma who responded to chemotherapy may not need radiation treatment.

Children with Hodgkin lymphoma who have favorable clinical features and who respond early to chemotherapy may not need treatment with radiation. The finding, reported in the June 27 JAMA, is from a clinical trial of 88 patients younger than 21 with low-risk disease.

Children who had an early complete response to the chemotherapy regimen used in the trial and who were not treated with radiation (as stipulated in the study protocol) had 5-year survival rates similar to those of children who did not have the same response to chemotherapy and therefore required radiation.  

"This study adds to evidence that it is possible to omit radiation even in patients treated with a less intense chemotherapy regimen and still achieve excellent long-term survival," lead investigator Dr. Monika Metzger of St. Jude Children's Research Hospital said in a statement.

Nine of 10 children with low-risk Hodgkin lymphoma survive the disease, but many will experience side effects of treatment later in life, including secondary cancers. Researchers and clinicians have been trying to identify patients for whom therapy can be refined and shortened so that they will suffer fewer long-term side effects.

This study adds to evidence that it is possible to omit radiation even in patients treated with a less intense chemotherapy regimen and still achieve excellent long-term survival.

—Dr. Monika Metzger

"We know we can cure Hodgkin lymphoma, but how do we cure it in a way that patients will have the healthiest lives?" Dr. Metzger said in an interview. "This study proved that it was safe to omit radiation" for certain patients.

In the nonrandomized phase II trial, 47 patients had a complete response to two cycles of combination chemotherapy known as the VAMP regimen; 41 patients did not have a complete response and therefore had radiation. The 88 patients were treated between 2000 and 2008 at St. Jude, Stanford University Medical Center, Dana-Farber Cancer Institute, Massachusetts General Hospital, and Maine Medical Center in Portland.

The patients were followed for a median of nearly 7 years. The 5-year event-free survival rates were 89.4 percent in the patients who received only chemotherapy, compared with 87.5 percent in the patients who received chemotherapy plus radiation.

These findings "highlight the continued commitment to reduce complications in the treatment of childhood malignancies," wrote Drs. Kimberly Whelan and Frederick Goldman of the University of Alabama at Birmingham in an accompanying editorial.

Five patients in the chemotherapy-only group experienced a relapse; all responded to salvage therapy with chemotherapy and radiation without the need for an autologous stem cell transplant. Four of these patients had a form of the disease called nodular lymphocyte-predominant Hodgkin lymphoma. The less intensive chemotherapy regimen may not be appropriate for children in this subgroup, the study authors noted.

Because the study population was relatively small, the authors had limited power to assess differences between study sites or to do subgroup analyses. "Thus, it would be important to confirm the results in a larger cohort," they wrote.

The emphasis on minimizing therapy when possible is especially important in the treatment of childhood malignancies.

—Drs. Kimberly Whelan and Frederick Goldman

Dr. Metzger and her colleagues are developing a treatment regimen for low-risk patients that involves lower doses of radiation therapy and would reduce the percentage of patients who undergo radiation therapy to less than the roughly 50 percent in the current study. "Clearly, the goal is to find the best balance between chemotherapy and radiation therapy," she said.

Older patients with Hodgkin lymphoma who have similarly limited forms of the disease and who are less able to tolerate intensive chemotherapy may also be candidates for the minimal treatment approach tested in this study, Dr. Metzger noted.

"The emphasis on minimizing therapy when possible is especially important in the treatment of childhood malignancies," the editorialists wrote. They cautioned, however, that "any attempt to decrease therapy to minimize late effects must be balanced with the risk of relapse because the primary cause of death the first 10 years after diagnosis remains recurrent disease."

Edward R. Winstead

Cancer Research Highlights

Test May Reduce the Need for Surgery to Diagnose Thyroid Cancer

A new test may spare some patients with suspicious thyroid nodules from diagnostic surgery. Researchers analyzed thyroid nodule samples collected via fine-needle aspiration (FNA) for the expression of a panel of 167 genes and found that the test accurately identified whether nodules were cancerous. Their results were published June 25 in the New England Journal of Medicine.

About 15 to 30 percent of patients undergoing FNA for suspicious thyroid nodules have indeterminate findings on standard cytology tests—that is, the tests show cellular changes that indicate a possible cancer but the findings are inconclusive. Although the majority of those with inconclusive cytology results have a benign condition, most have thyroid surgery to determine whether cancer is present.

Several researchers said the test has the potential to change clinical practice by eliminating or delaying the need for such surgery in some patients.

The researchers collected more than 4,800 aspirate samples from nearly 3,800 patients treated at 49 academic centers and community hospitals over a 19-month period. Of these, they analyzed indeterminate FNA samples from 265 nodules for which surgical samples were also available. The FNA samples were analyzed using the 167-gene panel that the researchers had developed based on earlier research.

Overall, when the results from the gene expression test were compared with diagnostic results from thyroid samples removed during surgery, the test correctly identified 92 percent of the malignant samples and 93 percent of the benign samples. But about half of the samples that the gene expression test identified as suspicious—not clearly malignant or clearly benign—were actually benign on surgical analysis.

For patients with indeterminate cytology results, the gene expression test "can be useful in making important [patient] management decisions, such as recommending watchful waiting in lieu of diagnostic surgery," wrote lead author Dr. Erik Alexander of Brigham and Women's Hospital and his colleagues.

Dr. Ann Gramza of NCI's Center for Cancer Research agreed. But she cautioned that "a negative result should not dismiss a patient from further follow-up surveillance of the nodule."

"The risk…is that 5 to 10 percent of nodules classified as benign...are likely to be malignant [false negatives], particularly those that are cytologically indeterminate but suggestive of cancer," wrote Dr. J. Larry Jameson of the University of Pennsylvania in an accompanying editorial. In such patients, he explained, "it might be reasonable" to do another FNA biopsy or perform a diagnostic surgical procedure.

One recent study, Dr. Jameson noted, suggested that the reduction in surgeries that could result from its use—about 25,000 fewer operations per year—"could result in substantial cost savings," even with the added cost of the test.

Skin Cancers Traced to Previously Unknown Effect of UV Radiation

The harmful effects of the sun on the outer layer of skin (the epidermis) are well documented. But ultraviolet (UV) radiation from the sun also may alter cells in the underlying layer of skin (the dermis), setting the stage for the development of cancer in the epidermis, according to findings published June 8 in Cell.

In the study, researchers observed epidermal changes in mice that were similar to those seen in UV-induced human premalignant skin lesions called actinic keratosis, which can progress to squamous cell carcinoma, the most common skin cancer in humans. In the mice, the Notch signaling pathway was lost in stromal cells, which contribute to the dermal compartment of the skin.

The loss of Notch signaling appeared to be sufficient for tumors to emerge in the overlying epidermis, the researchers observed. The increased inflammation that accompanied the loss of Notch signaling also may have played a role in tumor development, they added.

"This study says that changes in the stroma are as important as changes in the epidermis, and we probably need to pay attention to them," said lead investigator Dr. G. Paolo Dotto of Massachusetts General Hospital and the University of Lausanne, Switzerland.

To investigate the clinical relevance of the mouse findings, the researchers analyzed tissue from human patients with actinic keratosis. They found that Notch signaling was reduced in human stromal cells near precancerous lesions. Moreover, similar molecular changes were induced by UVA radiation, which is an environmental cause of skin cancer, the study authors noted.

The findings may provide insights into the phenomenon of field cancerization, in which a patch or field of cells, rather than a single initiating cell, changes when exposed to a carcinogen and has the potential to become premalignant, Dr. Dotto pointed out.

In an accompanying editorial, Drs. Sakari Vanharanta and Joan Massagué of Memorial Sloan-Kettering Cancer Center praised the study for raising the possibility that, in addition to causing mutations, UV radiation may lead to tumor-promoting changes in dermal cells.

The findings add to the extensive list of harmful effects of excessive sun exposure. "This should give [people] one more reason to cover up," wrote Drs. Vanharanta and Massagué.

Experimental Drug Based on Plant Toxin Targets and Kills Tumor Cells

Researchers have engineered a drug that can deliver a potent cell-killing toxin to tumors while largely sparing normal tissues. The drug, known as G202, shrank xenograft tumors of several human cancers in mice, including prostate, breast, kidney, and bladder cancer, and had relatively few toxic effects. On the basis of these findings, reported June 27 in Science Translational Medicine, researchers have initiated an early-phase clinical trial of G202 in patients with advanced cancer.

G202 delivers its toxic payload—a potent analog of the plant substance thapsigargin—to tumors by binding specifically to a protein known as prostate-specific membrane antigen (PSMA). PSMA is found in high levels in most prostate cancers. It is also found in tumor endothelial cells, which line blood vessels in a variety of solid tumors but not in normal endothelial cells. PSMA is an enzyme that spans the cell membrane and can cut proteins in specific places.

Researchers designed G202 so that it not only binds to PSMA but is also a target for PSMA's protein-cutting activity. G202 is an inactive "prodrug," and PSMA causes the release of the active, cell-killing thapsigargin analog from the prodrug form. This release takes place outside the cell, in the tumor microenvironment. Once released, the thapsigargin analog is taken up by nearby tumor cells, where it inhibits a protein known as the SERCA pump. Shutting down the SERCA pump floods the cell with calcium and triggers programmed cell death.

Unlike commonly used chemotherapy drugs, which typically work by killing rapidly dividing cells, "[thapsigargin] and its analogs can kill both rapidly proliferating and nonproliferating cells with equal potency," wrote Drs. Samuel Denmeade and John Isaacs of Johns Hopkins University and their colleagues. This ability, they noted, makes a thapsigargin-based drug particularly suitable for treating prostate cancer because most cancer cells in metastatic prostate cancer are not dividing.

Safety studies of G202 that are required before the drug can be tested in humans showed that it caused transient reversible kidney toxicity in rats and monkeys. G202 did not cause bone marrow toxicity—a common side effect of traditional cell-killing chemotherapy—in mice, rats, or monkeys.

Also in the Journals: Cells Most Vulnerable to HPV Identified

Researchers have identified a distinct population of cervical cells that are targeted by cancer-causing types of human papillomavirus (HPV), according to a study published June 26 in the Proceedings of the National Academy of Sciences.

These cells sit at the junction between the interior and exterior epithelial surfaces of the cervix and have a unique appearance and gene expression profile. The researchers showed that specific biomarkers of these junction cells were expressed in HPV-associated precancers and cancers. Forced expression of proteins coded for HPV (HPV oncoproteins) in other cell types did not cause the expression of junction cell biomarkers. And researchers did not find junction cell biomarkers in HPV-associated vaginal, vulvar, or penile precancers.

By examining tissue from women who had surgery to remove cervical tissue followed several months later by a hysterectomy, the researchers found that cells expressing the junction cell markers did not return once they were removed. These findings raise the possibility that removing junction cells may prevent cervical cancer, although further research is needed to understand how these cells change during a woman's life.

Guest Commentary by Dr. Julia H. Rowland

Survivorship icon

Cancer Survivorship Research: Translating Science to Care

Dr. Julia H. RowlandDr. Julia H. Rowland

As more than 500 researchers, patient advocates, cancer care specialists, public health officials, and others gathered outside Washington, DC, on June 14–16 for the Sixth Biennial Cancer Survivorship Research Conference, the American Cancer Society announced that an estimated 13.7 million people in the United States are living after a cancer diagnosis, and the estimated number of cancer survivors is expected to increase to almost 18 million by 2022.

These numbers, based on data from NCI's Surveillance, Epidemiology, and End Results Program, underscore the need for the biennial conference. The event, which began in 2002, brings together those involved in cancer survivorship research and the delivery of survivors' post-treatment care to discuss findings and to work together to advance the field.

The meeting is jointly sponsored by NCI's Office of Cancer Survivorship, the American Cancer Society's Behavioral Research Center, the Lance Armstrong Foundation, and the Centers for Disease Control and Prevention. As one speaker at the conference said, "With over 13 million survivors in the U.S., we need to get this right."

I looked forward to this year's conference with great enthusiasm, and my high expectations were surpassed. The conference theme, "Cancer Survivorship Research: Translating Science to Care," reflected the growing consensus about the importance of translating scientific discoveries into clinical and behavioral interventions and replicating the work across diverse populations.

We were fortunate to have Dr. Russell Glasgow, NCI's deputy director of Implementation Science, provide the "bookend" talks for this event. He launched the dialogue by walking the audience through the translational science process from basic scientific discovery to public health impact, and he challenged us to consider how we were going to move survivorship research along this pathway. Building on this theme, each plenary, special session, and symposium placed new findings along the "lab bench to park bench continuum" to stimulate thinking about how best to translate research into real-life practice.

The first plenary session focused on obesity, a national public health issue of particular concern to cancer survivors and their caregivers, given the increased likelihood of weight gain in some populations following a cancer diagnosis, as well as the increased health risks associated with obesity. Speakers presented new animal studies that are informing behavior change interventions for survivors who need them most, population studies demonstrating that obesity might not have the same effects on all survivors, and weight-control programs that have successfully reduced obesity in at-risk populations. (See the NCI Cancer Bulletin special issue on obesity and cancer research.)

A second plenary session explored issues related to health equity. In her introduction to this session, NCI's Dr. Shobha Srinivasan reminded the audience that we have a long way to go in addressing what she pointedly described as "avoidable inequalities."

Toward that end, Dr. Melinda Stolley of the University of Illinois at Chicago described a new weight-loss program, "Moving Forward Together." The program is tailored to the needs of African American breast cancer survivors, the majority of whom are obese or overweight at diagnosis and at risk for further weight gain when treated for cancer. In turn, UCLA's Dr. Jackie Casillas provided details of her collaboration with community partners to develop materials for a photonovella designed to promote awareness of survivors' needs and reduce the stigma attached to cancer in the Hispanic community. Dr. Linda Burhansstipanov reminded us that American Indian/Alaska Native survivors may be particularly vulnerable to adverse outcomes, due to the already high burden of comorbid diseases like diabetes in these populations.

A critical take-home message from this plenary was: We as researchers must work diligently to build programs that are sustainable and have a life after our study is done. And this challenge is especially important for work conducted with minority and medically underserved groups.

A final plenary emphasized the importance of communication and coordination during post-treatment care of cancer survivors. In this session, NCI researcher Dr. Neeraj Arora, who is also a cancer survivor, poignantly illustrated how a cancer survivor can feel "homeless in a world of medical homes." Survivors are often shuttled between primary care providers, oncologists, and other specialists whose medical expertise may become necessary as a result of the late effects of treatment, he explained, without any communication or coordination of care between these doctors.

Dr. Arora noted that the existence of multiple comorbidities compounds this problem in the older population, which actually composes the majority of cancer survivors today.

The conference's symposia and special sessions focused on the numerous targeted concerns of cancer survivors and those who care for them, including

  • stress, fatigue, cognitive, and cardiac effects of cancer treatment;
  • economic issues;
  • resilience (what enables some patients to better cope with a cancer diagnosis and the resulting treatment and after effects);
  • survivorship care planning;
  • adherence to treatment and after care;
  • communication within the family;
  • sexuality and relationships; and
  • the many other possible psychosocial effects of cancer survivorship.

The conference's translational framework helped participants in the biennial's special survivor/advocate program better understand the research under way, recent study results, and how the study findings can be put into practice to optimize physical and psychosocial functioning and prolong the lives of cancer survivors. At the same time, researchers at the conference gained invaluable insight into the needs and concerns of cancer survivors.

Dr. Glasgow closed the conference, summarizing the greatest tasks that stand before the cancer survivorship research community as we continue to design and conduct research, with an eye toward translating that research into high-quality, cost-effective care across populations. He pointed to the need for a balance between fidelity to evidence-based programs and adaptation to a local setting or population. He encouraged those of us in the cancer survivorship field to be good journalists and to ask: "Who, what, when, where, why, and how?"

Those of us in the field will remember these central questions as we address the needs of cancer survivors and bring better care to this ever-growing population.

Dr. Julia H. Rowland
Director, NCI Office of Cancer Survivorship


To Eat or Not to Eat: With Cancer Therapies, That Is the Question

Reader Suggested

When we are healthy, we tend to eat what we want, when we want, and without much thought about how our bodies process food and anything else we ingest. But what we eat and when we eat it can affect the way our bodies absorb and react to medications, sometimes to the extent of altering treatment outcomes.

Food intake, therefore, is an important variable when determining the optimal treatment for many diseases. And cancer researchers are now exploring whether manipulating food intake could help reduce the side effects of some treatments or make them more effective, as well as more cost-effective.

A Double Challenge to Cancer Cells

Medicine bottles with an apple in the foreground What we eat and when we eat it can affect the way the body absorbs and reacts to cancer treatments.

In 2008, the laboratory of Dr. Valter Longo, a professor of gerontology and biological science at the University of Southern California (USC), showed that fasting for 2 to 3 days protected normal cells in culture and mice with xenograft tumors from chemotherapy drugs without protecting cancer cells—an effect they called differential stress resistance.

Dr. Longo and oncologists from USC later published a study of 10 elderly cancer patients who voluntarily underwent short-term fasting before and/or after cytotoxic chemotherapy infusion. Patients reported fewer side effects, including fatigue, weakness, and gastrointestinal problems, when they fasted. However, some doctors still worried that fasting could also protect cancer cells, explained Dr. Longo, which would negate its use in cancer patients.

A recent study by the USC research team, published March 7 in Science Translational Medicine, addressed this concern by showing that, contrary to such fears, fasting renders cancer cells more sensitive to chemotherapy.

The researchers found that fasting conditions in cell culture and in mice caused normal and cancer cells to radically change their gene expression patterns—but in very different ways. Normal cells reduced the expression of genes associated with cell growth and division and diverted their energy to cellular maintenance pathways that protect normal cells from stressful conditions and repair stress-induced damage. In contrast, cancer cells reduced the expression of many protective genes, which made them more likely to die, explained Dr. Longo.

Fasting results in "more investment in a variety of systems that protect the [normal] cell," Dr. Longo said. This shift to maintenance (instead of growth) has an added benefit for normal cells: Nondividing cells that enter a maintenance mode are less likely to be damaged by chemotherapy drugs that target the process of cell division.

In contrast, cancer cells contain mutations that may hinder their ability to respond to starvation conditions by shifting their resources away from growth, as normal cells do. Fasting also deprives cancer cells of the glucose and other molecules they need to fuel their endless cell division. Therefore, fasting adds a second stressor on top of chemotherapy, forcing cancer cells to deal "with two extreme environments at once," explained Dr. Longo.

Fasting adds a second stressor on top of chemotherapy, forcing cancer cells to deal with two extreme environments at once.

—Dr. Valter Longo

This combination of stressors led to promising results in animal studies. In mice with implanted breast cancer cells, short-term fasting alone delayed tumor growth to the same extent as treatment with the drug cyclophosphamide. Fasting before administering the drug had a stronger effect: the tumors of fasting mice given cyclophosphamide grew to less than half the size of those in nonfasting mice. The researchers saw similar results in mice implanted with melanoma or glioma cells.

In mouse models of metastatic melanoma, breast cancer, and neuroblastoma, fasting combined with high-dose chemotherapy extended survival compared with high-dose chemotherapy without fasting. The combination also reduced the overall number of metastatic tumors. Moreover, 20 to 40 percent of fasting mice with neuroblastoma had a long-term remission, which was not observed in mice that received chemotherapy without fasting.

The USC team is now studying how fasting can reduce side effects in people receiving chemotherapy. Dr. Longo has helped design three ongoing early-phase clinical trials examining this question (at USC, the Mayo Clinic, and Leiden University in the Netherlands).

And a consortium of 12 hospitals in the United States and Europe is planning two trials, each with more than 800 patients, Dr. Longo noted. One trial will look at whether fasting can reduce chemotherapy side effects, and the other will look at whether fasting can influence both side effects and drug efficacy (as observed in mice).

According to a survey by the USC team, more than 70 percent of eligible patients would refuse a water-only fast, so the international trials will use a substitution diet called Chemolieve that the research team developed and commercially marketed under an NCI Small Business Innovation Research (SBIR) contract. The researchers designed the diet to provide a minimum amount of nutrients to cancer cells while providing nourishment to the patients, sparing them the discomfort of fasting.

Danger, But Also Opportunity

On the flip side of the coin, researchers at the University of Chicago are exploring whether the bioavailability of some oral cancer drugs—the amount of drug absorbed and used by the body—can be increased by taking the drugs with food.

For many oral drugs, whether a patient takes them with food is irrelevant. But some oral drugs have a clinically significant food effect, which means that taking them at the prescribed dose with food causes a substantial change in their bioavailability. If a food effect leads to a marked decrease in bioavailability, too little drug will reach the bloodstream. If a food effect leads to a large increase in bioavailability, patients taking the drug with food risk overdosing.

This second scenario is a concern for several oral cancer drugs, including nilotinib (Tasigna) for chronic myelogenous leukemia and lapatinib for advanced breast cancer. The risk of sudden cardiac death from taking nilotinib at its prescribed dose with food is so high that the manufacturer has included a boxed warning about the dangers and developed a corresponding risk evaluation and mitigation strategy.

Dr. Mark Ratain, professor of medicine at the University of Chicago, sees opportunity instead of danger in the food effect, as well as a major flaw in what has become the default strategy for oral cancer drug development.

Oral Cancer Drugs That Are More Potent When Taken with Food

Cancer DrugApproximate Increase in AUC*
When Taken with Food
Estimated Monthly Cost at the
Prescribed Dose (2011)
*AUC = area under the curve; a measurement used to estimate the bioavailability of drugs. (Data courtesy of Dr. Mark Ratain, University of Chicago)

For many noncancer drugs that have a greater bioavailability with food, that food effect has been exploited, explained Dr. Ratain. For example, drugs such as darunavir for HIV or telaprevir for hepatitis C are prescribed at lower doses to be taken with a meal.

In oncology, the opposite has happened. Discovery of a food effect has led to the development of a high prescribed dose to be given without food. "That's not convenient for patients" who may take these drugs for years and are otherwise healthy, said Dr. Ratain, such as patients with chronic myelogenous leukemia who achieve complete remission on nilotinib but who must continue taking the drug every day.

Testing oral oncology drugs that have a food effect at lower doses with food might substantially reduce side effects and costs, suggests Dr. Ratain. His research group is testing this concept in a phase II clinical trial of abiraterone acetate (Zytiga), approved for metastatic prostate cancer. Dr. Ratain and his colleagues are testing whether men can safely reduce their dose of the drug by 75 percent by taking it with food. And, in turn, reducing the dose might cut drug costs, he added.

Some oral drugs have what scientists call a clinically significant food effect—taking them at the prescribed dose with food causes either a major increase or decrease in bioavailability.

The researchers are randomly assigning participants to one of two treatment groups: the approved dose of 1,000 mg without food or 250 mg taken with a low-fat breakfast. The reduction in prostate-specific antigen (PSA), variability in pharmacokinetics, and effects on the hormonal targets of the drug will be compared between the two groups.

"When one is starting with a drug and wants to study the pharmacokinetics in healthy volunteers, the cleanest thing to do is to study [the drug during] fasting. But just because fasting potentially provides less variability in dose between patients, that doesn't mean it's the best way to administer any given drug," said Dr. Ratain. "We're asking questions that I think the FDA should require companies [to answer]—what is the variability [in dose] over time, with food and with fasting?"

This is beginning to happen. The FDA's Center for Drug Evaluation and Research (CDER) now recommends to all pharmaceutical sponsors that "the impact of food intake on oral oncology drugs should be assessed early in drug development—during the pre-Investigational New Drug (IND) and phase I development periods," said Dr. Atiqur Rahman of CDER's Office of Clinical Pharmacology.

"Information obtained from these evaluations should be incorporated in the phase II and phase III development trials to guide dosing recommendations with regard to food intake," he continued. CDER also informs the sponsors that studying food effect in the late phase of drug development may be necessary if the formulation or dosage is significantly altered from the one tested during early clinical development.

But "whether a particular oral oncology drug can be allowed to be developed with food will depend on many factors, such as the magnitude and variability of the food effect, the therapeutic window of the drug, as well as the characteristics of the disease and the patient population," Dr. Rahman concluded.

Sharon Reynolds

Featured Clinical Trial

MRI-Guided Focal Laser Therapy for Low-Risk Prostate Cancer

Name of the Trial
MRI-Guided Focal Therapy in Prostate Cancer (NCI-11-C-0158). See the protocol summary.

Dr. Peter Pinto Dr. Peter Pinto

Principal Investigator
Dr. Peter Pinto, NCI Center for Cancer Research

Why This Trial Is Important
Roughly 240,000 men will be diagnosed with prostate cancer in the United States this year. Most of them will receive their diagnosis after a prostate biopsy that was triggered by screening with the PSA test rather than by symptoms. Consequently, many of these men will have cancer that is confined to a small portion of the prostate gland (low-volume disease) and is likely to grow so slowly that it may never jeopardize their health (low-grade disease).

Management options for men with such low-risk prostate cancer include treatment and active surveillance, in which the cancer is monitored and treatment is delayed until there are signs of disease progression. Current treatment options include surgery to remove the prostate (radical prostatectomy) and radiation or ablation therapy to destroy the entire prostate gland. Although active surveillance may be recommended, most men seek immediate treatment.

Unfortunately, the available treatments target the entire prostate and often affect nearby nerves and muscles that help control urinary continence and erectile function. Because of the high likelihood of serious side effects and the typical slow course of prostate cancer growth, the U.S. Preventive Services Task Force recently recommended against routine PSA screening for men of any age. However, this recommendation has been questioned by many doctors and patient groups.

Given that PSA screening is unlikely to be abandoned in the short term and that many men diagnosed with low-risk disease will still seek treatment, researchers are eager to develop new approaches to treating low-volume, low-grade prostate cancer that carry less risk for serious side effects.

In this pilot study, which is being conducted at the NIH Clinical Center, men diagnosed with low-risk prostate cancer and men with suspected prostate cancer will undergo advanced magnetic-resonance imaging (MRI) techniques developed at NCI to visualize the prostate and tumor tissue in high detail and guide a biopsy to that area. The men will then be treated at a later date using MRI-guided focal laser ablation therapy to only the area of the prostate that has cancer. The study will assess the feasibility and safety of this therapy. 

"Some of the recommendations against PSA screening are based on data from large clinical trials conducted in both Europe and the United States which found that, to save one life from prostate cancer, you have to treat many men who then may suffer the harms of treatment," said Dr. Pinto. "We are trying to find a better way to treat prostate cancer without the side effects of traditional whole-prostate therapy.

"Our approach is to use focal therapy to treat only the area of the prostate where the tumor is. This involves inserting a laser fiber into the tumor nodule with MRI guidance, heating the tumor with a laser, and using MRI to watch in real-time as the heat from the laser destroys the tumor while leaving the remaining prostate gland intact and the surrounding nerves and muscles unharmed," he explained.

For More Information
See the lists of eligibility criteria and trial contact information or call the NCI Clinical Trials Referral Office at 1-888-NCI-1937. The call is toll free and confidential.

An archive of "Featured Clinical Trial" columns is available at

Community Update

A Meeting of Minds: Young Oncologists Make the Most of the ASCO Annual Meeting

Photo of the Trainees and Junior Faculty Member Lounge at the American Society of Clinical Oncology Annual Meeting (Photo by © ASCO/Scott Morgan 2012)Attendees gathered in the Trainees and Junior Faculty Member Lounge at the American Society of Clinical Oncology annual meeting. (Photo by © ASCO/Scott Morgan 2012)

Much of the cutting-edge research discussed each year at the American Society of Clinical Oncology (ASCO) annual meeting is presented by researchers just launching their careers.

Most display their work in one of the many poster sessions, while a select few give formal oral presentations. Either way, the meeting gives these young physician-scientists an opportunity to discuss and defend their data in one of the largest international forums for cancer research.

But navigating a meeting of roughly 31,000 oncology professionals and making the most of the experience can be a challenge.

"It's a huge conference, and no matter how much homework you do beforehand, it can be very overwhelming," said Dr. Ayca Gucalp, a third-year fellow in the Breast Cancer Medicine Service at Memorial Sloan-Kettering Cancer Center (MSKCC), who was attending ASCO for the second time. "Last year it was about learning [my way around], taking it all in, and meeting many of the investigators whose manuscripts I had read."

"It's just immense," agreed Dr. James Harding, a hematology and oncology fellow studying melanoma at MSKCC and a first-time ASCO attendee. "There are so many very established people here and a lot of interesting research happening. It's kind of hard to know where to go, but it's been exciting."

Those who have attended ASCO annual meetings before tend to arrive with a plan.  

The first time he attended the ASCO meeting, Dr. Andrew Weickhardt, a clinical fellow who studies lung cancer at the University of Colorado Cancer Center, said he attended only the oral presentations.

"The next time I realized that the poster sessions were really useful for meeting people and talking dynamically about research," the Australian native continued. "This time, I've found that some of the education sessions and the clinical science symposia, which I previously had ignored, were quite good in getting a bit more depth in some areas."

A Focus on Research

For this next generation of cancer investigators, attending the ASCO meeting is first and foremost about sharing their findings and discovering which new ideas are advancing their fields.

Attendees navigate the American Society of Clinical Oncology Annual Meeting. (Photo by © ASCO/Scott Morgan 2012) More than 31,000 people from more than 100 countries attended the 2012 ASCO annual meeting. (Photo by © ASCO/Scott Morgan 2012)

Although researchers may get a hint of which larger studies will be presented before the meeting from promotional material and press releases, the poster and oral abstract sessions can provide some surprises. Dr. Gucalp was pleased to see the five or so abstracts with a similar theme to her own work on the role of the androgen receptor signaling pathway in breast cancer development, which she discussed in an oral presentation.

"There's an excitement brewing about androgen receptor signaling in breast cancer, and so you feel like you're on the right track," she commented. "With the prostate cancer field having so many agents already available, there are numerous options available for investigation in breast cancer."

Presenting their work at an event the size of the ASCO annual meeting is also a good way for young researchers to get critical feedback on their data from experts.

Dr. Benjamin Maughan, a resident at the University of Utah Huntsman Cancer Institute and a recipient of a Conquer Cancer Foundation of ASCO Merit Award, presented a poster on alternative endpoints for clinical trials involving patients with urothelial carcinoma and found the process to be useful. "[The poster session] turned out really well," he wrote in an e-mail after the meeting. "I had quite a few meaningful discussions about this project and good feedback."

Face Time

But the ASCO meeting is about more than merely taking in the details of the latest clinical studies.

"The immediate importance of a lot of what is presented here can be grasped by reading an abstract book or looking at a virtual meeting; you can do that sitting in Australia or Uzbekistan," said Dr. Weickhardt. "What is important, I think, is actually meeting the people who do the research."

NCI Named One of the Best Places to Work for Postdocs

NCI ranked 13th on The Scientists' 2012 Best Places to Work for postdocs. Career development opportunities are one of the institute's strengths, according to the journal's 2012 survey. For information about training opportunities at NCI, visit the Center for Cancer Training website.

"The meeting has been a great opportunity to interact with other colleagues and to meet trainees from other centers," agreed Dr. Irene Brana of Princess Margaret Hospital in Toronto, who received a Young Investigator Award from the Conquer Cancer Foundation of ASCO for her research on biomarkers of response or resistance to combinations of targeted therapies in mice.

"I get to spend some time meeting the people that I've collaborated with," Dr. Gucalp said. "Sometimes they're in different countries, and this is the only common ground that we have to meet." She continued, "I've even further developed relationships [with people] in my own department. We're always so busy while we're at work, and this [meeting gives us] time to develop and talk about ideas."

The meeting also provides opportunities for fellows to learn about career options after training.

"I have gotten a lot from the career development modules," said Dr. Harding. "In one, they put together a panel of various practitioners: academics, community practitioners, and pharmaceutical representatives. To hear their stories, how they chose their paths, how they found mentors, and why they picked [the careers] they did, I think, is very important for someone at my level."

Although no events at the meeting were organized specifically for medical residents, Dr. Maughan was able to meet a number of fellows and program directors of institutions where he planned to apply for fellowships.

The ASCO Influence

Many of these young researchers identified their interest in oncology early on, while in medical school, and most plan to continue on the academic career path.

"I like the academic environment," said Dr. Harding, who also received a Young Investigator Award from the Conquer Cancer Foundation of ASCO. "As you can see from being at this meeting, [academia] is very stimulating and everyone has so many ideas; there's so much discussion."

ASCO sessions can even influence the research focus of an academic career.

Dr. Maughan originally was interested in pursuing gene therapy in advanced cancer patients. After attending a series of talks on clinical trial design to identify the best setting for a targeted breast cancer therapy, however, he decided that "clearly the best chance for a meaningful impact is in early therapy instead of late-term salvage therapy. It makes me rethink my approach to oncology research regarding gene therapy techniques."

Deciding where to start their independent careers is a critical aspect of their research success. Dr. Gucalp has accepted a faculty position at MSKCC and will continue developing some of the projects she started as a fellow, whereas Dr. Weickhardt is weighing a return to Australia.

Jennifer Crawford

FDA Update

FDA Approves Test to Aid Post-PSA Biopsy Decisions

The Food and Drug Administration (FDA) has approved a test to help men with elevated prostate-specific antigen (PSA) test scores decide whether to have a biopsy to test for prostate cancer.

The Access Hybritech p2PSA test is approved for use in men aged 50 or older who have a PSA test score between 4 and 10 ng/ml but who show no signs of cancer during a digital rectal exam.

A PSA test score between 4 and 10 ng/mL often prompts physicians to recommend a prostate biopsy. Most biopsies from men with PSA scores in that range, however, reveal no cancer or identify cancers that likely will never pose a health risk. And biopsies themselves have risks, including the risk of life-threatening infection.

The Access Hybritech p2PSA test measures a form of PSA called [-2]proPSA in the blood. Results from the test are combined with a PSA score and a measurement of free PSA to calculate the Prostate Health Index, or phi.

FDA approval was based on a clinical study of nearly 660 men, approximately half of whom had prostate cancer. In the study, the phi score was better able to distinguish between benign conditions and prostate cancer than the PSA score. The study also found that the probability of having prostate cancer detected following a biopsy rose as the phi score increased.

But the study was not designed to determine whether the phi test reduces the risk of dying of prostate cancer, noted Dr. Barry Kramer, director of NCI’s Division of Cancer Prevention.

Several earlier studies of the phi test, including a study sponsored by NCI’s Early Detection Research Network, have suggested that higher phi scores also may indicate more aggressive prostate cancer.

However, there is no standard phi score that indicates whether a biopsy should be performed, the FDA noted. “The choice of an appropriate…phi score to be used in guiding clinical decision-making may vary for each patient and may depend in part on other clinically important factors or on family history of disease,” the agency explained in its approval summary.

The Access Hybritech p2PSA will be available for sale in the United States later this year, according to Beckman Coulter, the company that developed the test. Update

Popular NCI Publications Now Available as E-Books

E-book reader

NCI is making some of its most popular patient education publications available to more users. These six e-books are currently available for free online:

NCI e-books are available in two formats, epub and mobi. Epub materials can be read on iPhones, iPads, Android phones and tablets, and on many other devices, including the Nook, Kobo, and Sony Reader. Mobi publications can be read on Kindle and other devices that have Mobipocket-compatible e-book readers. (Consult your device manual for information on how to load e-books onto your device.)

More titles are being developed as e-books and will be available soon. An up-to-date list of NCI e-books is available on the Publications Locator E-Book Editions Collection page.

NCI Mobile Website Rated among Top 10 Federal Apps

Government Computer News (GCN) has rated NCI's mobile site among the top 10 federal mobile apps, with a perfect score in two out of three areas rated. On a 10-point scale, garnered 10 points for "usefulness" and "ease of use" and 6 points for "coolness factor."

The site gives mobile users easy access to a dictionary of cancer terms, information by cancer type, and a wealth of resources on topics ranging from risk factors and possible causes of cancer to treatment and side effects. John Breeden, GCN lab director, noted, "[] will even give users helpful advice about what to ask their doctor in the event of a cancer diagnosis and suggest new treatment plans that your general practitioner may not yet be aware of.

"I wish [this tool] had been available when my late father was battling cancer," Breeden wrote. "It might have made us better prepared for the pitfalls along the way. Cancer seems to touch everyone in some way, and it's nice to have this app as a starting point if it's ever needed. It well deserves a usefulness rating of 10."


Free Workshop for Cancer Survivors: Managing Post-Treatment Neuropathy

Drs. Julie Silver, Christian Custodio, and Nessa Coyle Drs. Julie Silver, Christian Custodio, and Nessa Coyle

The tenth annual Cancer Survivorship Series, "Living With, Through, and Beyond Cancer," will hold the last of four workshops this year on July 17, 1:30–2:30 p.m. ET. This free series offers cancer survivors, their families, friends, and health care professionals practical information to help them cope with concerns and issues that arise after treatment ends.

Part IV of the series, "Managing Post-Treatment Neuropathy," will feature Dr. Julie Silver of Harvard Medical School, Dr. Christian Custodio of Memorial Sloan-Kettering Cancer Center and Weill Medical College of Cornell University, and Dr. Nessa Coyle, an independent consultant.

Participants can listen online or by telephone. To register, visit the workshop web page.

If you missed the first three workshops in the series, recordings are available online:

These workshops are presented by CancerCare, in collaboration with NCI, LIVESTRONG, the American Cancer Society, the Intercultural Cancer Council, Living Beyond Breast Cancer, and the National Coalition for Cancer Survivorship.

Funding Available to Support Collaborations between U.S. and Chinese Scientists

NIH and the National Natural Science Foundation of China (NSFC) recently published corresponding funding announcements to encourage and support research cooperation between U.S. and Chinese scientists in several research areas, including infection-related cancers. NIH released a request for applications for R01 research project grants for U.S. investigators, and NSFC published an announcement for new 3-year projects from Chinese collaborating investigators. This initiative is part of a U.S.–China Program for Biomedical Research Cooperation that was established by NIH and NSFC in 2010.

U.S. and Chinese investigators will work together to develop corresponding applications to NIH and NSFC. Both agencies will review applications in parallel using harmonized review criteria and make funding decisions according to the research priorities of both countries. NIH has pledged to support up to $5 million in total costs in FY 2012 under this program (up to $200,000 per year per project in total costs over a 3-year period). NSFC will support up to 3 million renminbi (about $472,000) for each 3-year project to support Chinese collaborators.