Tai chi could help overcome cognitive effects of chemotherapy, evidence suggests

ScienceDaily (June 7, 2011) — According to the American Cancer Society, more than 11.4 million Americans are currently living with cancer. While cancer treatments are plentiful, many have negative side effects. Previous studies have indicated that a significant number of patients who receive chemotherapy also experience cognitive declines, including decreases in verbal fluency and memory. Now, one University of Missouri health psychologist has found evidence that indicates Tai Chi, a Chinese martial art, might help overcome some of those problems.

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"Scientists have known for years that Tai Chi positively impacts physical and emotional health, but this small study also uncovered evidence that it might help cognitive functioning as well," said Stephanie Reid-Arndt, assistant professor and chair of the Department of Health Psychology in the School of Health Professions. "We know this activity can help people with their quality of life in general, and with this new study, we are encouraged about how Tai Chi could also help those who have received chemotherapy. I also hope this encourages more people to think about Tai Chi positively on a broader scale in their lives."

Tai Chi involves practicing slow motion routines and is based on several principles, including mindfulness, breathing awareness, active relaxation and slow movements. The emphasis on slow movement makes Tai Chi particularly suited to a wide range of fitness levels, which makes it very relevant for those who have had chemotherapy and might be experiencing physical limitations as a result, Reid-Arndt said.

The MU pilot study followed a group of women with a history of chemotherapy. The women participated in a 60-minute Tai Chi class two times a week for 10 weeks. The women were tested on memory, language, attention, stress, mood and fatigue before and after the 10-week sessions. According to Reid-Arndt, the results of the tests indicated that the women had made significant improvements in their psychological health and cognitive abilities.

"Tai Chi really helps individuals focus their attention, and this study also demonstrates how good Tai Chi could be for anyone, whether or not they have undergone treatment for cancer," Reid-Arndt said. "Due to the small size of this study, we really need to test a larger group of individuals to gain a better understanding of the specific benefits of this activity for patients who have been treated with chemotherapy and how significant these improvements might be."

The study was published recently in Complementary Therapies in Clinical Practice.

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Coffee drinking improves hepatitis C treatment response, study suggests

ScienceDaily (June 8, 2011) — Advanced hepatitis C patients with chronic liver disease may benefit from drinking coffee during treatment, according to a new study in Gastroenterology, the official journal of the American Gastroenterological Association (AGA) Institute. Patients who received peginterferon plus ribavirin treatment and who drank three or more cups of coffee per day were two times more likely to respond to treatment than non-drinkers.

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"Coffee intake has been associated with a lower level of liver enzymes, reduced progression of chronic liver disease and reduced incidence of liver cancer," said Neal Freedman, PhD, MPH, of the National Cancer Institute and lead author of this study. "Although we observed an independent association between coffee intake and virologic response to treatment, this association needs replication in other studies."

Among non-drinkers, 46 percent had an early virologic response; 26 percent had no detectable serum hepatitis C virus (HCV) ribonucleic acid at week 20; 22 percent had no detectable serum at week 48; and 11 percent had a sustained virologic response. In contrast, the corresponding proportions for those who drank three or more cups of coffee per day were 73 percent, 52 percent, 49 percent and 26 percent, respectively.

Approximately 70 to 80 percent of individuals exposed to HCV become chronically infected. Worldwide, these individuals are estimated to number between 130 and 170 million. Higher coffee consumption has been associated with slower progression of pre-existing liver disease and lower risk of liver cancer. However, the relationship with response to anti-HCV treatment had not been previously evaluated. Treatment with peginterferon and ribavirin resolves chronic hepatitis C in about half of patients. It is unknown whether coffee will improve response with the addition of new drugs that were recently approved for use in the U.S.

Because patients in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial also had previously failed interferon therapy, it is not clear whether the results can be generalized to other patient populations. Future studies among patients with less advanced disease, those who are treatment-naïve to prior therapy, or who are being treated with newer antiviral agents are needed.

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Less toxic combination of erlotinib and bevacizumab is effective non-small cell lung cancer patients, study suggests

ScienceDaily (June 1, 2011) — The standard treatment for patients with advanced non-small cell lung cancer (NSCLC) is a combination of two old-fashioned cytotoxic chemotherapy drugs. The combination, however, comes with substantial toxicity. Now, Fox Chase Cancer Center researchers report that a combination of two molecularly-targeted agents may provide similar therapeutic benefit with less toxicity.

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"These results seem to be better than standard of care," says Hossein Borghaei, DO, medical oncologist at Fox Chase, who will present the results at the 2011 Annual Meeting of the American Society of Clinical Oncology on June 4. "Of course, the problem with a phase II trial always is that the patients tend to be a select patient population. But when you look at the numbers, the patients appear to be benefiting from the treatment. They stay on treatment longer and the time to progression on average was a little bit better. And we don't have a lot of toxicities, like major hair loss or nausea, and we don't have a lot of neutropenia or anemia."

"So overall it looks like a well tolerated regimen and it appears to be an effective front-line therapy in this patient population," he says.

Until recently, clinicians assumed that older patients were more likely to suffer from serious toxicities associated with standard chemotherapy. Therefore, Borghaei's team focused their current study on patients 65 years and older, enrolling 33 patients with a median age of 74 years. All patients had previously untreated, advanced NSCLC. Patients received standard dose erlotinib (a small molecule inhibitor of the epidermal growth factor receptor) and bevacizumab (an antibody that blocks the vascular endothelial growth factor pathway) every 21 days until patients either progressed or stopped treatment due to adverse events.

Six patients remain on therapy and have received 4 to 40 cycles of treatment. Of the 24 patients off therapy, the median number of cycles received was 4, with a range of one to 40. The estimated progression-free survival for all patients is 6.6 months. The estimated one-year survival is 56.6%, with 12 patients remaining alive, and the estimated median overall survival is 14.1 months.

"With standard chemotherapy we can only give four to six cycles," Borghaei says. "But with this biologic regimen we can continue therapy because there is less toxicity. They are on continuous drugs, which might be one reason that they appear to have longer progression free survival. We have to wait for the final data and analyze it before we know -- and the big test would be a head-to-head phase III trial with chemotherapy."

The most common serious adverse events in the trial were grade 3 hypertension, which occurred in five patients, and grade 3 rash, which occurred in three patients. Additionally, the following grade 3 toxicities affected one patient each, fatigue, anorexia, neutropenia with infection, bowel perforation, and abnormal blood tests. Two patients had grade 3 diarrhea and one patient had grade 4 diarrhea.

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Two-thirds of newly diagnosed U.S. cancer patients unable to obtain oncology appointments, study suggests

ScienceDaily (June 1, 2011) — Newly diagnosed cancer patients frequently face hurdles in obtaining an appointment for care with an oncologist, according to new research from the Perelman School of Medicine at the University of Pennnsylvania that will be presented on June 4 at the 2011 annual meeting of American Society of Clinical Oncology. Even callers with private health insurance had difficulty scheduling an appointment, with just 22 percent of them obtaining a slot, compared to 29 percent of uninsured patients and 17 percent of patients on Medicaid, according to results of a study in which research assistants posed as patients seeking an initial evaluation.

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"Although healthcare reform is likely to expand health insurance coverage to more Americans, our research shows that even with insurance, patients face barriers when they try to access cancer care," says lead author Keerthi Gogineni, MD, an instructor in the division of Hematology-Oncology at Penn's Abramson Cancer Center. "Given the typical pre-appointment expectations for new patients -- which typically involve referral requirements, paperwork and routing of medical records and test results -- both insured and uninsured patients must contend with many challenges that delay care with a specialty cancer provider."

In the study, research assistants attempted to call 160 U.S. hospitals under three different circumstances each, varying only their insurance status as they explained their scripted patient situation, which involved a new diagnosis of an inoperable liver cancer. Callers reached a scheduler 79 percent of the time, but only 29 percent of those callers received appointments. Of the appointments ultimately scheduled, 35 percent required multiple calls to complete the process. In nearly a quarter of cases, callers failed to reach staff even after three attempts. Among reasons for denial of appointments or inability to schedule: Demand for medical records (39 percent), not being able to reach appropriate schedulers (24 percent), and referral requirements (18 percent).

The authors note that the access problems revealed in the study may become more urgent in the coming years, given Institute of Medicine and ASCO projections showing a widening gap between the number of people living with cancer and the number of practicing oncologists available to care for them.

Gogineni and her co-author, Katrina Armstrong, MD, MSCE, chief of the division of General Internal Medicine and associate director of Outcomes and Delivery in the Abramson Cancer Center, suggest that more patient navigator programs could play a critical role at coaching patients through this initial phase of their care. Since literacy issues or lack of guidance from a referring physician may impede patients' ability to locate the proper number to call for help at some hospitals, they also urge centers to train staff at locations other than appointment hotlines or intake centers to point new patients to the proper location.

"Patients who are newly diagnosed with cancer may be confused or frightened," Armstrong says. "Asking them to find their way through the complex process of obtaining imaging studies and other tests or collecting records from another doctor prior to scheduling an appointment may pose an undue burden, and cancer centers should be prepared to provide help with those preliminary steps."

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Antifungal drug delays need for chemo in advanced prostate cancer, study suggests

ScienceDaily (June 2, 2011) — The oral antifungal drug itraconazole, most commonly used to treat nail fungus, may keep prostate cancer from worsening and delay the need for chemotherapy in men with advanced disease. Details of the finding, from a clinical trial led by Johns Hopkins experts, are scheduled for presentation on June 4 at the 2011 American Society of Clinical Oncology (ASCO) annual meeting.

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Currently, the drug is approved to treat fungal infections in nails and other organs. Serious side effects can include heart failure, and Johns Hopkins experts caution that itraconazole needs further study before it can be considered for prostate cancer treatment.

Identified as a potential anticancer drug after Hopkins scientists scoured a database of more than 3,000 FDA-approved drugs, itraconazole appears to block tumor blood vessel growth -- the only drug in its class to do so -- much like the anticancer drug bevacizumab (Avastin). The antifungal also disrupts a key cancer-initiating biological pathway called Hedgehog. Laboratory testing by Johns Hopkins scientist Jun Liu, Ph.D., has shown that human prostate tumors implanted in mice shrink when treated with itraconazole.

"The most effective therapy we have right now for metastatic prostate cancer is hormone therapy, and when it doesn't work, the next step is usually chemotherapy," says Emmanuel Antonarakis, M.D., assistant professor of oncology at the Johns Hopkins Kimmel Cancer Center. In a search for compounds that could put off chemotherapy, the Johns Hopkins team turned to itraconazole.

For the study, patients with prostate cancer that had spread to other organs and did not respond to hormone therapy were randomly assigned to receive low or high doses of itraconazole.

Over 24 weeks of daily treatment with oral itraconazole, the investigators tracked the length of time for each patient's prostate cancer to worsen (called progression-free survival). Evidence of worsening disease was measured by a 25 percent increase in their blood level of prostate specific antigen (PSA), a marker for prostate cancer.

Early in the trial, preliminary analysis of 17 men receiving low doses of itraconazole showed that only two of them (11.8 percent) had stable or declining PSA. Because of the limited response, no further men were given low doses of the drug.

However, 11 of 24 (48.4 percent) men taking high doses of itraconazole had stable or declining PSA levels lasting at least 24 weeks. In addition, nearly a third of men taking the high dose had PSA reductions of 30 percent or more. Metastatic prostate cancer patients receiving no treatment typically would worsen in eight to 12 weeks, according to Antonarakis.

The investigators also found that 12 of 14 men taking high doses of itraconazole had lower levels of circulating tumor cells present in their blood after therapy, compared with their baseline levels.

Seven patients experienced side effects, including low potassium, hypertension and fluid retention, but the problems were resolved with potassium replacement pills, anti-hypertension drugs, and diuretics.

"We also tested whether itraconazole acted as hormone therapy by tracking levels of testosterone and DHEA (a testosterone derivative) in the blood, and we found no reductions of either testosterone or DHEA," says Antonarakis. "This finding shows that itraconazole is not just another hormone therapy, and has a unique mechanism of action."

Antonarakis and colleagues next plan to examine blood and skin samples taken from study participants specifically to look for levels of proteins linked to tumor blood vessel formation and the Hedgehog pathway.

"With these results, we believe that high-dose itraconazole is worth studying in a larger group of men with advanced prostate cancer," adds Antonarakis.

The clinical trial was funded by the Department of Defense (DoD) Prostate Cancer Research Program, the Commonwealth Foundation for Cancer Research, the David H. Koch Charitable Foundation, a 2009 American Society of Clinical Oncology (ASCO) Young Investigator Award granted to Antonarakis, and the National Institutes of Health/National Cancer Institute.

In addition to Antonarakis, other investigators participating in the research on behalf of the Prostate Cancer Clinical Trials Consortium included Amanda Blackford, Serina King, Anja Frost, Seun Ajiboye, Sushant Kachhap, Michelle Rudek, and Michael Carducci from Johns Hopkins; Elisabeth Heath from the Karmanos Cancer Institute; David Smith from University of Michigan, Ann Arbor; and Dana Rathkopf and Daniel Danila from Memorial Sloan Kettering Cancer Center.

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Shave biopsy is a safe and acceptable method for initial evaluation of melanoma, study suggests

ScienceDaily (May 23, 2011) — A shave biopsy is a reasonably safe and accurate method for the initial diagnosis of melanoma, according to a study published in the April issue of the Journal of the American College of Surgeons. In the past, some physicians have criticized shave biopsies for not providing accurate T (tumor) stage information, thereby complicating treatment planning.

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"We conducted this study to determine the impact of shave biopsies on the initial staging of melanoma and their impact on the final treatment planning for patients," explained Jonathan S. Zager, MD, FACS, associate professor at the Moffitt Cancer Center, Tampa, FL, and lead author of the study. "Shave biopsies are commonly used by dermatologists, primary care physicians, and surgeons as a less invasive and more efficient means of biopsying suspicious lesions for diagnosis."

In the largest study to date, researchers at Moffitt Cancer Center and the University of Florida Shands Cancer Center, Gainesville, retrospectively analyzed 600 consecutive patients who underwent a shave biopsy for suspicious skin lesions between 2006 and 2009. They found presumptive pre-shave diagnosis of melanoma was suspected in only 25 percent of these patients. After definitive surgical wide excision was performed, 133 (22 percent) had residual melanoma in the surgical excision specimen. However, the detection of residual melanoma in these patients only resulted in subsequent upstaging in T-stage in a small group of 18 (3 percent) patients, showing that T-stage and depth data obtained through shave biopsy were accurate in 97 percent of all patients.

"The diagnosis of melanoma can be extremely challenging, even for the most experienced health care professional," Dr. Zager said. "Although traditional excisional biopsy remains the gold standard for the diagnosis of suspicious skin lesions, where a rim of normal appearing skin can be excised with the specimen (especially when melanoma is suspected), our results show shave biopsies may be used as a first-line evaluation for skin lesions with minimal impact on T-staging and definitive treatment options."

While there are advantages and disadvantages to consider when comparing excisional, punch, and shave biopsies of skin lesions, the disadvantages of shave biopsies remain largely cosmetic. Because shave biopsies don't require sutures for closure, a depressed, hypopigmented or hyperpigmented scar may sometimes occur. Punch biopsies present physicians with limitations with regard to the size of the biopsy tools available to accommodate an accurate biopsy, as best practices generally recommend excision of some normal appearing skin at the edges of the skin lesion in question.

According to the American Cancer Society, skin cancer accounts for almost half of all cancers in the United States. Melanoma, the most severe form of skin cancer, affected about 68,130 people in 2010 alone.

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Breast cancer linked to obesity gene, new research suggests

ScienceDaily (May 23, 2011) — New research aimed to better identify the genetic factors that lead to breast cancer has uncovered a link between the fat mass and obesity associated gene (FTO) and a higher incidence of breast cancer. According to the study conducted at Northwestern Memorial Hospital, people who possess a variant of the FTO gene have up to a 30 percent greater chance of developing breast cancer. Research to identify why the link exists is ongoing, but experts say the finding takes us one step closer to personalized medicine based on genetic risk which would allow for better monitoring and prevention of illness, as well as targeted treatment.

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"This is a fascinating early finding, which fits with the known connections between obesity and breast cancer," said Virginia Kaklamani, MD, oncologist at Northwestern Memorial, co-director of the Cancer Genetics Program at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and lead author of the study.

Each individual carries the FTO gene, but only 18 percent have this variant of the gene. Kaklamani, who specializes in cancer genetics, says testing for the FTO variant is not available currently, but it may be available in the future, similar to how genetic testing for the BRCA gene mutation exists today.

"Ten years ago we didn't know about the BRCA gene mutation which has been linked to breast and ovarian cancer. Today, we offer genetic testing and a specialized clinic for those at risk in order to minimize their risk and detect any indication of cancer early," said Kaklamani, who is also an associate professor of medicine at Northwestern University Feinberg School of Medicine. "This knowledge helps us better identify who is at an increased risk so one day, we can counter that risk through preventative measures and advanced screening."

The research, published in BMC Medical Genetics is part of an ongoing group of studies to further knowledge of genetic risk factors for breast cancer.

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Lipofilling may be safe during conservation treatment for breast cancer, study suggests

ScienceDaily (May 24, 2011) — A new study has gone some way to answering the question about whether or not a technique called lipofilling is safe for women who are having their breasts reconstructed after surgery for breast cancer.

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Lipofilling involves taking some fat from another area of a woman's body, such as her abdomen, and using it to fill in small defects or asymmetry that may occur during breast reconstruction. However, until now, there has been a lack of evidence as to whether or not the technique could trigger a recurrence of the original breast cancer, and so plastic surgeons have not been able to advise patients fully on the pros and cons of lipofilling, despite the fact that it has been used for over 30 years.

Now, a study published in the cancer journal Annals of Oncology suggests that lipofilling seems to be a safe procedure for breast cancer patients, although the authors say that longer follow-up and more research is required in order to confirm their findings.

The researchers analysed data on 321 women who had been operated on for primary breast cancer at the European Institute of Oncology (IEO) in Milan, Italy, between 1997 and 2008, and who had then had lipofilling as part of their breast reconstruction. These women were matched with double the number (642) of women who had also had surgery for primary breast cancer, but who did not undergo lipofilling.

The researchers followed up the women for an average of 56 months from the time of the primary surgery and 26 months from the lipofilling. They found that eight women in the lipofillling group and 19 women in the control group had a local recurrence of their cancer -- a difference that was not statistically significant. When they analysed the data to look specifically at recurrences in women with non-invasive cancer (in situ cancer) they found there were three cases of recurrence in the lipofilling group and none in the control group; this was statistically significant, but may have been affected by the very small numbers involved, the short follow-up and the fact that there were no recurrences in the control group despite previous research suggesting there should be an average recurrence rate of over two percent during this period of time. "This indicates there might have been some bias in the selection of the women with non-invasive breast cancer in the control group," explained one of the authors, Professor Jean Yves Petit.

Prof Petit, from the Division of Plastic Surgery at the IEO in Milan, said: "To date, only a few studies have focused on cancer recurrences after lipofilling, and this is the first case-control study to investigate the question and the first publication to show the safety of the procedure. Our overall results do not find any difference in recurrences between the women in the lipofilling and control groups. However, it is still too early in the follow-up to be able to draw any definitive conclusions. We urge other teams working in the same field to gather their own results concerning local recurrences after lipofilling in breast conservation treatment."

This study is important because other, experimental work in the laboratory has shown that fatty tissue is capable of producing growth factors that can trigger cancer cells to multiply. This raised the question of whether this might happen in humans.

"Work by other researchers has shown that secretions from transplanted fat tissues can stimulate angiogenesis

Vulnerability to nicotine addiction appears to have a genetic basis, study suggests

ScienceDaily (May 13, 2011) — A person's vulnerability to nicotine addiction appears to have a genetic basis, at least in part. A region in the midbrain called the habenula (from Latin: small reins) plays a key role in this process, as Dr. Inés Ibañez-Tallon and her team from the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany, have now shown. They also shed light on the mechanism that underlies addiction to nicotine.

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According to the World Health Organization WHO in Geneva, it is estimated that tobacco use kills more than five million people each year worldwide. Many of them die of lung cancer. "Two years ago, studies indicated that genetic variations in a specific gene cluster are risk factors for nicotine dependence and lung cancer," Dr. Ibañez-Tallon pointed out. She and her team, together with researchers from the Pasteur Institute in Paris, France and the Russian Academy of Sciences in Moscow, have now elucidated the mechanism underlying this dependence.

They investigated a specific receptor for the neurotransmitter acetylcholine, which is activated by nicotine in smokers and is encoded by this specific gene cluster, consisting of three subunits, that is three genes. "Although this gene cluster is present in the DNA of every cell, the receptor is only expressed in a few restricted areas of the brain. One of them is the habenula in the midbrain," Dr. Ibañez-Tallon explained.

The MDC researchers investigated this receptor and its subunits in egg cells of the African clawed frog (Xenopus laevis) and in transgenic mice. One of the three genes of the cluster is alpha5. "An important percentage of heavy smokers carry a single mutation in this gene. They are more prone to become addicted to nicotine and to develop lung cancer than individuals without this mutation," Dr. Ibañez-Tallon said.

Strong Aversion to Nicotine

A second gene in the gene cluster encoding this receptor is beta4. The MDC researchers demonstrated that transgenic mice expressing high levels of the beta4 gene have increased sensitivity to nicotine. These mice have a strong aversion to drinking water containing nicotine.

However, when the researchers expressed the mutated variant of the alpha5 gene via a lentivirus in the habenular brain region of these mice, after only two weeks the mice showed a preference for nicotine. Dr. Ibañez-Tallon and her colleagues conclude that only a balanced activity of these two genes can rein in nicotine use.

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Advanced-stage prostate cancer patients experience 20-year survival rates with surgery, study suggests

ScienceDaily (May 15, 2011) — Long-term survival rates for patients with advanced prostate cancer suggest they can be good candidates for surgery, Mayo Clinic researchers have found. Their study found a 20-year survival rate for 80 percent of patients diagnosed with cancer that has potentially spread beyond the prostate, known as cT3 prostate cancer, and treated with radical prostatectomy, or surgery to remove the prostate gland. Previously, patients found to have cT3 prostate cancer were offered radiation or hormone treatment, but not radical prostatectomy.

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The researchers presented their findings during the American Urological Association Annual Meeting in Washington.

"We are doing a much better job of identifying and expanding candidates for surgery, which results in better, longer outcomes for so many of our patients," says R. Jeffrey Karnes, M.D., of Mayo Clinic's Department of Urology. "We have confirmed that patients diagnosed with locally advanced prostate cancer can enjoy a long, cancer-free interval."

The 80 percent survival rate for cT3 diagnoses at 20 years compares to 90 percent for cT2, or cancer confined to the prostate. This long-term follow-up of patients who underwent surgery between 1987 and 1997 is an important advance in understanding the quality outcomes for cT3 patients. The study sample included patients diagnosed and operated on between 1987 and 1997. Ongoing research will examine contemporary data.

Other study investigators include Christopher Mitchell, M.D., Eric Umbreit, M.D., Rachel Carlson and Laureano Rangel, all of Mayo Clinic.

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