A phase III study has shown that adding an antibody-based therapy that harnesses the body’s immune system resulted in a 20 percent increase in the number of children living disease-free for at least two years with neuroblastoma. Neuroblastoma, a hard-to-treat cancer arising from nervous system cells, is responsible for 15 percent of cancer-related deaths in children. The researchers reported their findings - the first to show that immunotherapy could be effective against childhood cancer - online May 14, 2009 on the American Society of Clinical Oncology website in advance of presentation June 2.

“This establishes a new standard of care for a traditionally very difficult cancer in children,” said lead author Alice Yu, MD, PhD, professor of pediatric hematology/oncology at the University of California, San Diego School of Medicine and the Moores UCSD Cancer Center. “High-risk neuroblastoma has always been a frustrating cancer to treat because, despite aggressive therapy, it has a high relapse rate.”

The therapy targets a specific glycan (a complex sugar chain found on the surface of cells) on neuroblastoma cells called GD2, which inhibit the immune system from killing cancer cells. The antibody - ch14.18 - binds to this glycan, enabling various types of immune cells to attack the cancer.

Neuroblastoma - in which the cancer cells arise from nerve cells in the neck, chest, or abdomen - is the most common cancer diagnosed in the first year of life. Approximately 650 new cases of neuroblastoma are diagnosed in this country every year, and about 40 percent of patients have high-risk neuroblastoma. These high-risk patients are usually treated with surgery, intensive chemotherapy with stem cell rescue (in which patients’ adult stem cells, removed before treatment, are returned after chemotherapy to restore the blood and immune system), and radiation therapy. Still, only 30 percent of patients survive.

Yu and her colleagues compared both the percentage of patients who were still alive without experiencing a recurrence after two years as well as overall survival in two groups of 113 patients each. Patients began the trial when they were newly diagnosed with high-risk neuroblastoma. After conventional treatment with surgery, chemotherapy, stem cell rescue and radiotherapy, one group was given the standard treatment (retinoic acid) plus immunotherapy (the antibody plus immune-boosting substances), while 113 similar patients received the standard treatment alone.

After two years, 66 percent of individuals in the immunotherapy group were living free of cancer compared to 46 percent in the standard treatment group. Overall survival improved significantly as well. The trial patient randomization was halted early because of the benefit seen, and all patients enrolled in the trial will receive immunotherapy plus standard treatment.

Yu noted that the two-year mark is especially important because past trials have shown that those neuroblastoma patients who live without disease for two years after a stem cell transplant will most likely be cured.

“This is the first time in many years that we have been able to improve the ‘cure rate’ for neuroblastoma patients,” she said. “This new therapy can help us improve care and perhaps offer new hope to many patients and families.”

Yu and her team conducted the early phase I and phase II trials at the General Clinical Research Center at UC San Diego Medical Center.

Other co-authors include Andrew Gilman, Carolinas Medical Centre; M. Fevzi Ozkaynak, New York Medical College; Susan Cohn, University of Chicago; John Maris, Children’s Hospital of Philadelphia; Paul Sondel, University of Wisconsin; W. B. London, University of Florida; S. Kreissman, Duke University; H.X. Chen, National Cancer Institute; and K.K. Matthay, UCSD. Local patients were seen in San Diego at Rady Children’s Hospital.

Source:
Steve Benowitz

University of California - San Diego

There are many ways to deal with the pain of giving birth, but women and their obstetricians can always benefit from having another choice. A Cochrane review has concluded that women in labor should have the option of using transcutaneous electrical nerve stimulation (TENS) a non-drug method of pain management.

“There is only limited evidence that TENS reduces pain in labor and it does not seem to have any negative or positive impact on other outcomes for mothers and babies. However the majority of women in the reported studies have indicated that they would be willing to use TENS for a subsequent pregnancy,” said Tina Lavender, a review co-author and a professor of midwifery at the University of Manchester, in England.

Widely used in other areas of medicine, the TENS unit is a small device that emits low- voltage electrical pulses through electrodes attached to the body. The exact way the pulses work is unknown, but they are thought to block pain transmission by stimulating nerve pathways in the spinal cord. During labor, clinicians usually place the electrodes on the lower back, but they can also attach them at acupuncture points or to the head.

For the review, researchers analyzed 19 randomized controlled studies that examined the use of TENS during labor. The studies involved 1,671 women and occurred in 11 countries, with three studies in the United States. Fifteen studies examined TENS applied to the back, two to acupuncture points and two to the head. Studies compared TENS use to routine care, to the use of a sham TENS unit or to other types of pain management, either medications or other techniques.

Women in labor who received TENS were less likely to say they had severe pain compared to the other women. However, this difference was not great and was not consistent across the studies, nor did the studies show that women receiving TENS were more satisfied with their pain relief than those who did not use TENS.

The new review appears in the latest issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews like this one draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

Lavender and her colleagues noted that it is possible that using TENS gave the women a feeling of control over their pain and served as a distraction. They concluded that women should have the option of using it during labor, with or without other forms of pain management.

No one has data on how widespread the use of TENS in obstetrics is, Lavender said, noting that one British study found that about 16 percent of low-risk women having their first baby used TENS during their labor. Generally, TENS works with other forms of pain management during labor, such as epidural anesthetics.

“TENS is not widely used in the U.S., largely because the pain relief offered is modest and TENS units are not frequently available on labor and delivery units,” said Laura Goetzl, M.D., an associate professor of obstetrics and oncology at the Medical University of South Carolina, in Charleston.

“There is no barrier to patients arranging for a TENS unit for themselves and using it in labor; however, the cost to the patient may not be worth the benefit over other treatments that are more likely to be covered by her insurance,” she said. Obstetricians usually support any method of pain relief a woman wants to use as long as it is not harmful to the mother or her baby and as long as it does not conflict with the policies of the admitting hospital, Goetzl said.

TENS units are not expensive, about 30 British pounds to rent and 50 pounds to buy in the United Kingdom, according to Lavender, and about $50 to $80 to rent for a week in the United States, according to an Internet search.

Source: Health Behavior News Service

A landmark follow-up study found that heart attack survivors who receive implanted cardioverter defribillators (ICDs) live longer the longer they have them, according to the results of late-breaking clinical trail presented at the annual Scientific Sessions of the Heart Rhythm Society.

ICDs are devices designed to correct arrhythmias, electrical malfunctions that throw the heart out of rhythm and cause many of the sudden cardiac deaths each year in the United States. Most fatal arrhythmias in the aging are caused by scar tissue left behind by heart attacks that interferes with the heart’s electrical system.

The study that first tested the effectiveness of ICDs, the 2002 MADIT II trial (Multicenter Automatic Defibrillator Implantation Trial II), changed medical guidelines nationwide and made thousands of heart attack survivors eligible for ICD therapy. Led by Arthur Moss, M.D., professor of Medicine in the Department of Medicine at the University of Rochester Medical Center, the study found that the devices reduced risk of sudden cardiac death by 31 percent in heart attack survivors. At the same time, the ICD therapy could extend the average patient’s life by about two months over a follow-up period that averaged about 2 years per patient. While that survival benefit was meaningful to patients, some critics argued that it did not make sense for the healthcare system to pay for $25,000 a device that provided a modest extension of life in patients with chronic cardiac disease.

The current study watched the same patients for eight years, and found that over that time, patients with ICDs implant lived an average of more than a year longer, “greatly amplifying” the value of the treatment and arguing that it is dramatically more cost effective as a chronic therapy. Specifically, the new study found that MADIT II patients who had an ICD for eight years had a 37 percent lower chance of death from any cause than those without one, which translates into 1.2 life-years saved.

“These results show that ICDs extend the long-term survival of patients with life-threatening of heart conditions,” said Ilan Goldenberg, M.D., research associate professor within the Heart Research Follow-up Program at the University of Rochester Medical Center, and lead author of the new study. “These results emphasize the life-saving value of ICDs as chronic therapy for high-risk cardiac patients.

Source:
Greg Williams

University of Rochester Medical Center