Effect of obesity on patients with advanced non-small cell lung cancer

Obesity increases health risks for many things. Researchers wanted to know the impact of obesity on outcomes of patients with advanced non-small cell lung cancer. In the September issue of the International Association for the Study of Lung Cancer’s journal, the Journal of Thoracic Oncology (JTO), researchers conclude that obese patients had superior outcomes early on in the study, but then experienced increased hazards.

During the period from 1993 to 2004, the Eastern Cooperative Oncology Group enrolled 2684 patients to three phase III trials of first-line systemic chemotherapy for advanced NSCLC. At a median follow-up of 64.9 months, 2585 of the patients were declared eligible and included in this research. The patients had their body mass index (BMI) calculated. Consistent with the general population, 4.6 percent of patients were underweight, 44.1 percent were normal weight, 34.3 percent of patients were classified as overweight, and 16.9 percent were obese.

The median overall survival estimated among underweight patients was 7.0 months, among normal weight patients was 8.6 months, among overweight patients was 9.3 months and among obese patients was 11.0 months.

In multivariable models, obese patients had significantly different overall survival when compared with normal-weight and overweight patients; however, their risk of death from any cause increased dramatically once they had been on study longer than 16 months.

Researchers says, “this indicates that the protective effect of obesity in lung cancer patients is for a limited time, after which the ultimate impact of obesity on survival from all causes supersedes.”

Dahlberg et al., (2013). Body Mass Index and Its Association with Clinical Outcomes for Advanced Non-Small-Cell Lung Cancer Patients Enrolled on Eastern Cooperative Oncology Group Clinical Trials. J.Thoracic Oncol., EPub Ahead of Print [Abstract]

 

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Technique filters cancer where chemo can’t reach

A cancer therapy that removes malignant cells from a patient’s cerebrospinal fluid may soon be available to prevent metastases and decrease complications of cancers involving the brain, according to Penn State medical researchers.

Many cancer types metastasize to the brain — including breast cancer, pancreatic cancer, prostate cancer and leukemia — but by filtering these malignant cells out of the cerebrospinal fluid (CSF), the researchers hope to decrease the chance of cancer spreading toward and away from the brain.

The brain and spinal cord are surrounded by cerebrospinal fluid, separated from the blood circulating throughout the rest of the body by a cellular lining known as the blood-brain barrier.

“Most chemotherapies have a difficult time crossing the blood-brain barrier, but cancer cells can if they have the right instructions,” said Joshua E. Allen, postdoctoral fellow at the Penn State Hershey Cancer Institute.

The researchers have devised a way to move CSF through a filter outside the body that catches the cancer cells and then allows the CSF to flow back into the patient, tumor cell-free.

“Currently nothing exists that can filter cerebrospinal fluid — which, in some patients, contains malignant active cancer cells,” said Akshal S. Patel, neurosurgery resident at the Penn State Milton S. Hershey Medical Center. “This therapy filters all cerebrospinal fluid.”

Many treatments, including chemotherapy, increase therapeutic resistance of cancer cells, Allen noted. However, filtering cells out does not offer the malignant cells an opportunity to develop therapeutic resistance.

Treatment providers can count the cells captured in the filter and use that to measure the severity of metastasis, another benefit to using this method.

Approximately 15 to 20 percent of metastatic breast cancer patients eventually develop brain metastases, according to the researchers.

“There is a high likelihood of breast cancer patients getting cancer cells in their cerebrospinal fluid,” said Patel.

The researchers monitored the number of tumor cells in nine breast cancer patients with confirmed metastatic spread to their central nervous system. They counted both the number of tumor cells in the bloodstream and in the CSF.

Approximately half of these patients had tumor cells that moved through the blood-brain barrier. Allen and Patel found that this movement of tumor cells is not necessarily restricted to later phases of breast cancer, as previously thought.

With this new knowledge in mind, the researchers’ proposed method can help treat breast cancer — and other metastasizing cancers — earlier and with potentially fewer drugs. This filtering of body fluid is similar to that used as standard care for leukemia, and offers potentially increased cure rates.

“The minimum this therapy would provide is straining the tumor cells out,” said Allen. “But we could also include other therapies when returning the CSF to the body.”

A provisional patent application for this method described by the inventors has been filed.

Cancer ‘prehabilitation’ can reduce complications and improve treatment outcomes

Time between diagnosis and treatment provides ‘window of opportunity’ to optimize health

For patients with cancer, “prehabilitation”— interventions given between the time of diagnosis and the start of treatment—has the potential to reduce complications from treatments and improve physical and mental health outcomes, according to a report in the August American Journal of Physical Medicine & Rehabilitation, the official journal of the Association of Academic Physiatrists.

“A growing body of evidence supports preparing newly diagnosed cancer patients for and optimizing their health before starting acute treatments,” write Drs. Julie K. Silver and Jennifer Baima of Harvard Medical School. Their article, titled Cancer Prehabilitation: An Opportunity to Decrease Treatment-Related Morbidity, Increase Cancer Treatment Options, and Improve Physical and Psychological Health Outcomes, is the first comprehensive review of the topic.

“There is a rather long and impressive history of using prehabilitation to improve orthopedic surgical outcomes,” Dr. Silver comments. “Our new review shows that there is a unique opportunity to help many people who have been newly diagnosed with cancer to improve their physical and emotional outcomes.”

Cancer Prehabilitation—Getting Patients in Best Possible Shape for Treatment

The goal of cancer prehabilitation is to prevent or lessen the severity of anticipated treatment-related problems that could lead to later disability. Immediately after diagnosis, patients undergo physical and psychological assessments to establish their baseline level of function and identify any current impairment, and provide targeted interventions to reduce the risk and severity of future impairments.

Traditionally, pretreatment interventions focused on aerobic conditioning to build patients’ general strength and stamina. But recent studies have shown that more directed interventions can improve outcomes in patients with specific cancers: for example, swallowing exercises before surgery for head or neck cancer, smoking cessation to improve breathing function before lung cancer surgery, or pelvic floor exercises to reduce problems with urinary incontinence after surgery for prostate cancer.

Some studies have shown that prehabilitation interventions, individually or in combination, can increase the range of treatment options, lower complication rates, and improve physical and mental health outcomes. Benefits include a reduced risk of hospital readmission and lower health care costs.

Cancer prehabilitation seems more effective when it includes both physical and psychological interventions. Providing psychosocial support immediately after diagnosis has improved treatment outcomes for patients with prostate, breast, and ovarian cancer. Future studies may show that prehabilitation can increase patients’ ability to complete their recommended treatment—thus improving their chances of survival.

Drs. Silver and Baima emphasize that cancer prehabilitation should follow an individualized approach, “identifying current and anticipating future impairments as a critical first step in improving healthcare outcomes and decreasing costs.” They liken cancer prehabilitation to a puzzle, with individual approaches put together in combinations that best meet the needs of the individual patient.

While patients may fear that delaying cancer treatment may reduce their risk of survival, there’s typically some waiting period before treatment begins. This time—whether it’s a few days or a few weeks—may provide a “window of opportunity” for prehabilitation interventions to address physical and psychological issues. Drs. Silver and Baima write, “Newly diagnosed cancer patients are often seeking ways to become immediately involved in their care that may go beyond decision making about upcoming treatments.”

Studies have begun to show that physical and psychological prehabilitation interventions can reduce treatment-related complications, decrease length of hospital stay and/or readmissions, increase available treatment options for patients who would not otherwise be candidates, and quickly facilitate return of patients to the highest level of function possible. Drs. Silver and Baima highlight the need for further studies to identify the most effective prehabilitation interventions: “those that improve patient health outcomes and reduce direct and indirect healthcare costs.”

“This review provides an exciting ‘jumping-off point’ for cancer researchers to look more closely at how to improve outcomes from the moment of diagnosis onward,” Dr. Silver adds. “We hope it will serve to highlight this exciting area of research and to show clinicians that there are key opportunities right now to improve cancer care.”

Silver and Baima (2013). Cancer prehabilitation: An opportunity to decrease treatment-related morbidity, increase cancer treatment options, and improve physical and psychological health outcomes. Amer. J. Phys. Med. Rehab.92: 715-727 doi: 10.1097/PHM.0b013e31829b4afe [Article]

Epoetin alfa reduces anemia in breast cancer patients with no negative impact on survival

In patients with high-risk breast cancer, addition of the erythropoiesis-stimulating agent (ESA) epoetin alfa to the chemotherapy regimen may help avoid the decrease in hemoglobin levels and resulting anemia often seen in these patients and does not negatively affect relapse-free (RFS) or overall survival (OS). However, it can increase the risk of thrombotic events, according to a study published in the Journal of the National Cancer Institute.

To investigate the safety and efficacy of epoetin alfa, Volker Moebus, M.D., of the Department of Gynecology and Obstetrics, at the Klinikum Frankfurt Höchst in Frankfurt, Germany, and colleagues, conducted a second randomized study of patients in the intense dose-dense (IDD) chemotherapy arm of the AGO-ETC trial. Of 643 patients receiving the sequential chemotherapy regimen of epirubicin, paclitaxel, and cyclophosphamide, 324 were randomly assigned to receive the ESA epoetin alfa and 319 were assigned to the non-ESA group. The authors compared change in hemoglobin level, percentage of subjects requiring red blood cell (RBC) transfusion, incidence of thrombotic events, and, after a median follow-up of 62 months, OS, RFS and intra-mammary relapse in the two groups.

The researchers found that the patients in the non-ESA group had statistically significant reduction in hemoglobin levels and required more RBC transfusions than those in the ESA treatment group (28.1% vs 12.8%). ESA treatment had no impact on OS, RFS or intra-mammary relapse. However, patients treated with epoetin alfa were approximately twice as likely to experience thrombotic events compared with patients in the non-ESA group (7% vs 3%). The authors conclude that “ESAs appear to be safe drugs for the treatment of chemotherapy-induced anemia in patients with IDD chemotherapy regimens.”

In an accompanying editorial, Chau Dang, M.D., Clifford Hudis, M.D., and Larry Norton, M.D., of the Memorial Sloan-Kettering Cancer Center in NY, write that the study of Moebus et al. “provides important evidence that ESAs may be safe in the curative treatment of cancer.” However, they cite some limitations of the study, ie, a much larger sample size would be needed to unequivocally conclude that epoetin alfa had no effect on OS or RFS; the still unacceptably high transfusion rate (13%) in the ESA group; the high cost of ESAs given that they do not improve OS or RFS, and the approximately two-fold rate of thromboembolic events in the ESA group.

In a second editorial, Brian Leyland-Jones, M.B. B.S., Ph.D., of Edith Sanford Breast Cancer Research in SD, attempted to put this article into the context of the significant controversy surrounding this field, in terms of the effect of ESAs on overall survival, tumor progression and risk of thrombosis. He especially focused on trials where ESAs were prescribed within label. He noted that these drugs are powerful pharmacological tools, and in an era dominated by personalized medicine, should be prescribed according to individualized risk-benefit ratio.

Moebus et al., (2013). Adding epoetin alfa to intense dose-dense adjuvant chemotherapy for breast cancer: Randomized clinical trial. J. Natl. Cancer Inst., 105: 1018-1026 [Article]

Voices Against Brain Cancer Commends Neuropsychologist and Team for Research on Cognitive Brain-Training for Cancer Survivors

Ember Branch

 

Voices Against Brain CancerNew York, NY – July 15, 2013 – On July 12, Voices Against Brain Cancer, an organization dedicated to brain cancer research and advocacy, commends Shelli Kesler, a Stanford University clinical neuropsychologist, and her colleagues for using brain-training software to help lift the mental fog caused by cancer treatment.

 

According to a July 2nd, 2013 Medcitynews.com article entitled “Brain-training software may help lift ‘chemo fog’ cause by cancer treatment,” “Chemo fog” is a mental fuzziness induced by repeated cancer treatment. Researchers say cognitive brain exercises can improve brain function and ease the effects of the recurring chemotherapy.

 

Researchers went on to say that “those who used a brain-training program for 12 weeks were more cognitively flexible, more verbally fluent, and faster-thinking than survivors who didn’t train.”

 

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Menopause symptoms worse in cancer survivors

Cancer survivors were twice as likely to experience severe menopausal symptoms compared to women who have not had cancer, a new Australian study has found.

The study ( published in Menopause, the Journal of the North American Menopause Society) was led by the University of Melbourne and the Royal Women’s Hospital Melbourne, with the King Edward Memorial Hospital and the University of Western Australia.

Lead author, Dr Jennifer Marino of the University of Melbourne and the Royal Women’s Hospital said the study was the biggest of its kind to assess the impact of menopausal symptoms on the quality of life of cancer survivors.

“Our study showed for the first time, that cancer survivors experienced more severe and frequent menopausal symptoms (such as hot flushes and night sweats) than patients who did not have cancer,” Dr Marino said.

More than 151,000 (around one in 25) women in Australia are cancer survivors with more than one third of those are breast cancer survivors.

Almost 1,000 cancer survivors (mostly breast cancer) and 155 non-cancer patients aged 40 to 60, who attended the Menopause Symptoms After Cancer Clinic at the King Edward Memorial Hospital in Western Australia, were surveyed to determine a range of factors including severity of menopausal symptoms, impact on quality of life and sexual function.

Cancer survivors had twice as many hot flushes (six compared with three in 24 hours) and were twice as likely to report severe or very severe flushes as non-cancer patients. More than 200 cancer survivors reported experiencing more than 10 flushes a day.

Interestingly, the mental health of cancer survivors appeared to be better than the non-cancer patients.

“The study revealed the cancer survivors were less troubled by symptoms of anxiety and depression than women attending the menopause service who had never had cancer,” Dr Marino said.

Senior author Professor Martha Hickey said menopausal symptoms were a frequent and distressing effect of cancer treatments in women.

“In women with hormone sensitive cancer such as breast cancer, effective treatments reduce estrogen levels and this commonly leads to menopausal symptoms,” she said.

Co-author Professor Christobel Saunders, Deputy Head of the University of Western Australia School of Surgery, said the findings were significant in providing an improved understanding of the nature and impact of menopause on cancer survivors while also highlighting the need for better support services for menopausal women without cancer.

Marino et al., (2013). Nature and severity of menopausal symptoms and their impact on quality of life and sexual function in cancer survivors compared with women without a cancer history. Menopause, EPub Ahead of Print doi:10.1097/GME.0b013e3182976f46 [Abstract]

Ovarian cancer metastases influenced by factors in target tissues

Both milky spots and fat cells in omentum promote cancer cell migration, growth and spread.

Cancer researchers have wondered why ovarian cancer cells are so attracted to the abdominal cavity, especially the omentum, with the hope that such an understanding could lead to better disease management or even prevention. Results from a series of experiments suggest a two-step model of omental colonization in which i) cancer cells are attracted to and lodge within immune cell-containing structures known as milky spots, and ii) fat storage cells (adipocytes) fuel cancer cell growth and spread. This study is scheduled for publication in the August 2013 issue of The American Journal of Pathology.

The omentum is a large fatty structure that drapes off the stomach and blankets the peritoneal organs. Omental fat is composed of adipocytes, blood vessels, immune cells, and other connective tissue and contains unusual immune cell-containing structures known as milky spots, which play a key role in many of its protective functions. In previous research, investigators focused either on the milky spots or the adipocytes as key to attracting metastatic ovarian cancer cells. The results of the current experiments show that “although there are clear strengths to both of these models, neither address the intimate and dynamic interaction among milky spots, surrounding adipocytes, and other components of omental tissues. We propose an alternative, more fully integrated model,” says Carrie Rinker-Schaeffer, PhD, a professor in the Departments of Surgery (Section of Urology) and Obstetrics and Gynecology at The University of Chicago.

In the first experiment, researchers investigated whether abdominal fat tissue that contains milky spots is a more attractive target for cancer cells than abdominal fat that does not contain milky spots. This study took advantage of the fact that mice have a second source of milky spot-containing abdominal fat (splenoportal fat) as well as fat that is devoid of milky spots (the gonadal, uterine, and mesenteric fat). They found that different ovarian cancer cell lines (mouse derived ID8, and human derived SKOV3ip.1, HeyA8, and CaOV3) specifically colonize omental and splenoportal fat, forming large lesions of cancer cells within milky spots. In contrast, ovarian cancer cells were rarely detected in abdominal fat that lacks milky spots.

The rapid localization of ovarian cancer cells to milky spots indicated that omental tissue secretes a factor, or factors that attract the cancer cells to these structures. Experiments showed that milky-spot-containing tissues in particular can condition cell growth medium to stimulate the migration of cancer cells. This study found that cell medium conditioned by omenta and splenoportal fat caused a 95-fold increase in cell migration, compared to controls. This study also examined mice with specific immunodeficiencies to show that ovarian cancer cell colonization of milky spots is not affected by deficiency or absence of T cells, B cells, and/or NK cells.

The authors also found an inverse relationship between ovarian cancer cell growth and depletion of adipocytes. “These data are consistent with previous reports from other investigators that indicate cancer cells use lipids stored in adipocytes as an energy source for their continued growth,” says Dr. Rinker-Schaeffer. “Certain tumor cells (the ‘seed’) have a proclivity for specific organ microenvironments (the ‘soil’),” adds Dr. Rinker-Schaeffer. “Pioneers of metastasis research appreciated that the unique tissue architecture, physiology, and function of the target organ are essential to understanding metastatic organ specificity. With this in mind, we hope that our findings and discussion of how they fit into the big picture of omental colonization will facilitate studies that continue to improve our understanding of this process.”

In 2012, ovarian cancer was diagnosed in almost 23,000 American women and 16,000 died from the disease. It is estimated that 22,240 women will be diagnosed with and 14,030 women will die of cancer of the ovary in 2013.

Clark et al., (2013). Milky spots promote ovarian cancer metastatic colonization of peritoneal adipose in experimental models, Am. J. Pathol., Epub Ahead of Print.