Monday 23 December 2013

Next post - January 2, 2014




Top Canadian Cancer Society funded research stories of 2013

Research funded by the Canadian Cancer Society will ultimately change cancer forever. This page represents some of the most high-impact research of 2013 and highlights the breadth of research supported by the Society's donors. Read more here.

Cancer immunology named 'Breakthrough of the Year'

Cancer immunology has been selected as the "Breakthrough of the Year" by the editors of Science, the flagship journal of the American Association for the Advancement of Science. "Immunotherapy marks an entirely different way of treating cancer — by targeting the immune system, not the tumor itself," according to the report. It beat out scientific advances in areas such as human stem cells from cloning and the understanding of sleep. Read more here. (First time users may be asked to sign in.)

Report mentioned: Couzin-Frankel J. Breakthrough of the year 2013. Cancer immunotherapy. Science. 2013 Dec 20;342(6165):1432-3. PMID: 24357284

Muscle-invasive and non-muscle invasive bladder cancers arise from different stem cells

A University of Colorado Cancer Center study shows that progenitor cells that create MI bladder cancer are different than the progenitor cells that create NMI bladder cancer. Though these two cancers grow at the same site, they are different diseases. “This work provides an important new perspective on how we look at bladder cancer biology,” says Dan Theodorescu, MD, PhD, director of the University of Colorado Cancer Center and the study’s senior author. Read more here.

Study mentioned: Dancik GM, et al. A cell of origin gene signature indicates human bladder cancer has distinct cellular progenitors. Stem Cells. 2013 Dec 19. [Epub ahead of print] PMID: 24357085

Angelina Jolie's preventive mastectomy raised awareness, but not knowledge of breast cancer risk

Angelina Jolie heightened awareness about breast cancer when she announced in a New York Times op-ed that she had undergone a preventive double mastectomy. But a new study led by researchers in the University of Maryland School of Public Health and the Johns Hopkins School of Public Health reveals that widespread awareness of Jolie's story did not unfortunately translate into increased understanding of breast cancer risk. Read more here.

Study mentioned: Borzekowski DL, et al. The Angelina effect: immediate reach, grasp, and impact of going public. Genet Med. 2013 Dec 19. [Epub ahead of print] PMID: 24357847

Renegades of cell biology: why K-Ras gene mutations prove so deadly in cancer

Cells with a mutation in the gene called K-Ras—found in close to 30 percent of all cancers, but mostly those with worst prognosis, such as pancreatic cancer, colon cancer, and lung cancer—behave in ways that subvert the normal mechanisms of cell death, according to a cell-culture study by researchers from Huntsman Cancer Institute (HCI) at the University of Utah. Normal cells need survival signals from the tissue that surrounds them to remain alive. Other research has shown cells with the K-Ras mutation can survive and direct their own fate without these signals. Read more here.

Study mentioned: Slattum G, et al. Autophagy in Oncogenic K-Ras Promotes Basal Extrusion of Epithelial Cells by Degrading S1P. Current Biology, online 19 December 2013.

Friday 20 December 2013

Advances in stem cell transplantation strategies show promise to improve availability, success

Hematopoietic stem cell transplantation, once considered an effective yet risky alternative to drug therapy for blood cancer, has become more accessible and successful in a wide range of patients as a result of major advances in transplant strategies and technologies. Several studies representing these advances were presented during the 55th American Society of Hematology Annual Meeting and Exposition in New Orleans. Read more here.

Economic factors may affect getting guideline-recommended breast cancer treatment

Women with interruptions in health insurance coverage or with low income levels had a significantly increased likelihood of failing to receive breast cancer care that is in concordance with recommended treatment guidelines, according to results presented at the Sixth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved. Read more here.

Novel method could help bring cancer biomarkers to clinic

An international team of scientists led by Fred Hutchinson Cancer Research Center cancer proteomics expert Amanda Paulovich, M.D., has demonstrated the feasibility of large-scale, standardized protein measurements, which are necessary for validation of disease biomarkers and drug targets. The study shows that the scientists' targeted protein-detection approach has the potential to systematically and reliably measure the entire human repertoire of proteins, known as the proteome. Read more here.

Study mentioned: Kennedy JJ, et al. Demonstrating the feasibility of large-scale development of standardized assays to quantify human proteins. Nat Methods. 2013 Dec 8. [Epub ahead of print] PMID: 24317253

Novel drug regimen can improve stem cell transplantation outcomes

Adding bortezomib (Velcade) to standard preventive therapy for graft-versus-host-disease (GVHD) results in improved outcomes for patients receiving stem cell transplants from mismatched and unrelated donors, according to researchers from Dana-Farber Cancer Institute. In a new phase 2 trial, patients treated with bortezomib had lower rates of severe acute GVHD and treatment-related mortality, and experienced better one-year overall survival than has been seen historically with such patients receiving standard preventive therapy, the investigators reported at the American Society of Hematology annual meeting. Read more here.

Potential biological factor contributing to racial disparities in prostate cancer

Researchers have uncovered a potential biological factor that may contribute to disparities in prostate cancer incidence and mortality between African-American and non-Hispanic white men in the United States, according to results presented at the Sixth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved. Read more here.

New studies demonstrate that modified T cells are effective in treating blood-borne cancers

At the 2013 American Society of Hematology meeting in Dec. 2013, James Kochenderfer, M.D., investigator in the Experimental Transplantation and Immunology Branch, NCI, presented findings from two clinical trials evaluating the use of genetically modified immune system T cells as cancer therapy. Read more here.

Drug-antibody pair has promising activity in non-Hodgkin lymphoma

A toxin linked to a targeted monoclonal antibody has shown "compelling" antitumor activity in patients with non-Hodgkin lymphomas who were no longer responding to treatment, according to a report from Dana-Farber Cancer Institute. The ongoing open-label phase 2 study presented at the American Society of Hematology meeting was designed to test the activity of brentuximab vedotin (Adcetris) in relapsed or refractory non-Hodgkin lymphoma including B-cell cancers such as diffuse large B cell lymphoma. Read more here.

Less painful drug delivery for pediatric leukemia patients is safe, effective

Children with acute lymphoblastic leukemia, the most common form of pediatric cancer, can safely receive intravenous infusions of a reformulated mainstay of chemotherapy that has been delivered via painful intramuscular injection for more than 40 years, research suggests. Findings from the study, DFCI ALL Consortium Protocol 05-001, were presented at the 55th annual meeting of the American Society of Hematology. Read more here.

Screening decisions must balance potential benefits with potential patient harms

Screening to detect medical conditions has become standard practice for many diseases, but insufficient attention has been paid to the potential for harm, according to research conducted at the University of North Carolina. Read more here.

Study mentioned: Harris RP, et al. The Harms of Screening: A Proposed Taxonomy and Application to Lung Cancer Screening. JAMA Intern Med. 2013 Dec 9. [Epub ahead of print] PMID: 24322781

Thursday 19 December 2013

FDA: Nipple aspirate test no substitute for mammogram

The US Food and Drug Administration (FDA) is alerting women and their doctors not to use nipple aspirate tests in place of mammograms or other tests that screen for or diagnose breast cancer. The FDA says there is so far no scientific evidence that this test by itself can detect breast cancer or any other breast condition. Read more here.

View the FDA consumer update here.

Systems medicine paves the way for improved treatment for AML patients

A multidisciplinary team of researchers at the Institute for Molecular Medicine Finland (FIMM), and the Helsinki University Central Hospital has developed a novel individualised systems medicine strategy which enables selection of potentially effective cancer therapies for individual patients. Furthermore, this strategy helps in understanding and predicting drug resistance and may pave a path for individualised optimisation of patient therapies in the clinic for various types of cancers. Read more here.

Study mentioned: Pemovska T, et al. Individualized systems medicine strategy to tailor treatments for patients with chemorefractory acute myeloid leukemia. Cancer Discov. 2013 Dec;3(12):1416-29. PMID: 24056683

Wednesday 18 December 2013

Gene sequencing project finds family of drugs with promise for treating childhood tumor

Drugs that enhance a process called oxidative stress were found to kill rhabdomyosarcoma tumor cells growing in the laboratory and possibly bolstered the effectiveness of chemotherapy against this aggressive tumor of muscle and other soft tissue. The findings are the latest from the St. Jude Children’s Research Hospital–Washington University Pediatric Cancer Genome Project. Read more here.

Study mentioned: Chen X, et al. Targeting oxidative stress in embryonal rhabdomyosarcoma. Cancer Cell. 2013 Dec 9;24(6):710-24. PMID: 24332040

Multi-gene test could help spot breast cancer patients most at risk

A new test has the potential to help physicians identify patients with the most lethal forms of triple-negative breast cancer, a disease which requires aggressive and innovative treatment. The test was able to distinguish between patients with a good or poor prognosis, even within groups of patients already stratified by existing tests such as MammaPrint and Oncotype, as well as to extend its predictions to patients with more advanced or difficult-to-treat cancers. Read more here.

Study mentioned: Lee U, et al. A Prognostic Gene Signature for Metastasis-Free Survival of Triple Negative Breast Cancer Patients. PLoS ONE. 2013; 8(12): e82125.

Combined therapy linked to lower chance of recurrence in women with small, HER2-positive breast cancers

In a new study, women with relatively small, HER2-positive breast tumors who received a combination of lower-intensity chemotherapy and a targeted therapy following surgery or radiation therapy were very unlikely to have the cancer recur within a few years of treatment, investigators at Dana-Farber Cancer Institute and other research centers reported at the 2013 San Antonio Breast Cancer Symposium. Read more here.

Study identifies highly effective treatment option for patients with HER2-positive breast cancer

Combining the chemotherapy drugs docetaxel and carboplatin with the HER2-targeted therapy trastuzumab was identified to be an ideal postsurgery treatment option for patients with HER2-positive breast cancer, regardless of tumor size and whether or not disease has spread to the lymph nodes, according to results from the BETH study presented at the 2013 San Antonio Breast Cancer Symposium. Read more here.

Changing chemo not beneficial for metastatic B.C. patients with elevated circulating tumor cells

For women with metastatic breast cancer who had elevated amounts of circulating tumor cells in their blood after a first line of chemotherapy, switching immediately to a different chemotherapy did not improve overall survival or time to progression, according to the results of a phase III clinical trial presented at the 2013 San Antonio Breast Cancer Symposium. Read more here.

Pain drugs used in prostate gland removal linked to cancer outcome

The methods used to anesthetize prostate cancer patients and control pain when their prostate glands are surgically removed for adenocarcinoma may affect their long-term cancer outcomes, a study led by Mayo Clinic has found. Opioids, painkillers commonly given during and after surgery, may suppress the immune system's ability to fight cancer cells. Read more here.

Study mentioned: Scavonetto F, et al. Association between neuraxial analgesia, cancer progression, and mortality after radical prostatectomy: a large, retrospective matched cohort study. Br J Anaesth (2013) First published online: December 16, 2013

Misunderstanding of palliative care leads to preventable suffering

A new review says palliative care’s association with end of life has created an “identity problem” that means the majority of patients facing a serious illness do not benefit from treatment of the physical and psychological symptoms that occur throughout their disease. The authors say palliative care should be initiated at the same time as standard medical care for patients with serious illnesses, and not brought up only after treatment has failed. Read more here.

Study mentioned: Parikh RB, et al. Early specialty palliative care - translating data in oncology into practice. N Engl J Med. 2013 Dec 12;369(24):2347-51. PMID: 24328469

Tuesday 17 December 2013

New presurgery combination therapy may improve outcomes for women with triple-negative breast cancer

The I-SPY 2 trial, an innovative, multidrug, phase II breast cancer trial, has yielded positive results with the first drug to complete testing in the trial. Adding the chemotherapy carboplatin and the molecularly targeted drug veliparib to standard presurgery chemotherapy improved outcomes for women with triple-negative breast cancer, according to results from the I-SPY 2 trial presented at the 2013 San Antonio Breast Cancer Symposium. Read more here.

Ibrutinib and rituximab trigger 95 percent response rate among CLL patients

Nearly all of the high-risk chronic lymphocytic leukemia patients in a phase II clinical trial responded to treatment with the targeted therapy ibrutinib and the antibody rituximab, researchers reported at the 55th Annual Meeting of the American Society of Hematology. Read more here.

New models of drug-resistant breast cancer point to better treatments

Human breast tumors transplanted into mice are excellent models of metastatic cancer and are providing insights into how to attack breast cancers that no longer respond to the drugs used to treat them, according to research from Washington University School of Medicine in St. Louis. Read more here.

Additional drug shows promise for women with triple-negative breast cancer

In a nationwide study of women with triple-negative breast cancer, adding the chemotherapy drug carboplatin or the angiogenesis inhibitor Avastin to standard chemotherapy drugs brought a sharp increase in the number of patients whose tumors shrank away completely, investigators reported at the 2013 San Antonio Breast Cancer Symposium. Read more here.

Annual report: Cancer death rates in the US continue to decline

The rate of death from cancer in the United States continues to decline among both men and women, among all major racial and ethnic groups, and for the most common types of cancer, including lung, colon, breast, and prostate. The Annual Report to the Nation on the Status of Cancer shows that the death rate from all cancers combined is continuing the decline that began in the early 1990s. The report’s special feature section focuses on the ways other medical conditions impact survival among people with the most common types of cancer. Read more here.

Read the report, Annual Report to the Nation on the status of cancer, 1975-2010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer, here.

A study of anastrozole in breast cancer chemoprevention

Five years of treatment with a potent, non-steroidal aromatase inhibitor, anastrozole, reduced the incidence of primary breast cancer in postmenopausal women at high risk for developing the disease, according to an analysis of the international, double-blind, randomised placebo controlled study. The results were presented at the 2013 San Antonio Breast Cancer Symposium (10-14 December) and published simultaneously in the journal Lancet. Read more here.

Study mentioned: Cuzick J, et al. Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial. The Lancet, Early Online Publication, 12 December 2013.

Obinutuzumab/chlorambucil in the first-line treatment of older CLL patients

Obinutuzumab/chlorambucil is superior to rituximab/chlorambucil in the first-line treatment of older patients with chronic lymphocytic leukaemia (CLL) suffering from comorbidities. Obinutuzumab/chlorambucil combination led to a prolongation in progression-free survival which was the study primary endpoint. Secondary efficacy endpoints of higher response rate and minimal residual disease negativity rate were also achieved. Prolonged overall survival was seen when compared obinutuzumab/chlorambucil vs. chlorambucil alone. The final results of the phase III CLL11 trial were presented during a Plenary Session at the 55th American Society of Hematology (ASH) Annual Meeting (7-10 December 2013, New Orleans, USA). Read more here.

Monday 16 December 2013

New resources highlight the need for culturally safe cancer care in First Nations communities

While cancer affects everyone, rates of common cancers have increased among First Nations, Inuit and Métis people in the past few decades and in some populations are now at or above those in the general Canadian population. A new report released today examines cancer control for First Nations across Canada and provides a baseline against which progress can be measured over the coming years. Read more here.

Bones benefit from exercise after breast cancer

A new study conducted at the Oregon Health and Science University indicates that regular exercise helps maintain bone strength and prevent fractures in older breast cancer survivors. Study investigators measured "bone mineral density in the hip and spine, muscle and fat levels, and maximum upper and lower body strength." These findings support the notion that exercise programs for improving musculoskeletal health should be implemented in long-term care plans for breast cancer survivors. To read more about this study, click here. Study mentioned: Dobek J, Winters-Stone KM, Bennett JA, Nail L. Musculoskeletal changes after 1 year of exercise in older breast cancer survivors. J Cancer Surviv. 2013 Dec 7 [Epub ahead of print]. PMID: 24317968

Friday 13 December 2013

Study explores romantic struggles of cancer survivors

A Calgary researcher is looking at how cancer treatment impacts the way teens develop their sexual identities and romantic relationship skills. “We really think it’s important to take a look at adolescents and how it is that they, in the face of cancer, are able to obtain sexual knowledge, begin sexual exploration and more importantly develop a sense of themselves,” says Nancy Moules, a researcher with the Alberta Children’s Hospital Research Institute. Read more here.

Thursday 12 December 2013

Global cancer burden rises to 14.1 million new cases in 2012

The International Agency for Research on Cancer has released the latest data on
cancer incidence, mortality, and prevalence worldwide. The new version of IARC’s online database, GLOBOCAN 2012, provides the most recent estimates for 28 types of cancer in 184 countries worldwide and offers a comprehensive overview of the global cancer burden. Read more here.

Visit the GLOBOCAN website here.

Phase III study of idelalisib and rituximab for previously treated patients with chronic lymphocytic leukaemia

A phase III randomised, double-blind, placebo-controlled study evaluating idelalisib in combination with rituximab in previously treated chronic lymphocytic leukaemia patients who were not fit for chemotherapy demonstrated statistically significant improvement with acceptable safety over placebo plus rituximab in term of progression-free survival, overall response rate, lymph node response and overall survival. The benefit was observed even in heavily pretreated patients, including those with adverse genetic features. The results were presented in the Late-Breaking Abstracts Session of the 55th Annual Meeting of the American Society of Hematology in New Orleans (7-10 December, 2013). Read more here.

Wednesday 11 December 2013

CALR mutations in myeloproliferative neoplasms

Mutant CALR is a novel, specific molecular marker detected in majority of patients with myeloproliferative neoplasms who are negative for JAK2 and MPL mutations. Use of this marker in the clinic may improve diagnostic and therapeutic decision making in these patients, according to the late-breaking abstract results presented at the 55th Annual Meeting of American Society of Hematology (ASH) in New Orleans, USA (7-10 December, 2013). Read more here.

Mammogram controversy ‘artificial,’ study says

Many experts are closer to agreement over the benefit of mammograms than they realize, according to research presented at the San Antonio Breast Cancer Symposium. American Cancer Society Senior Director of Cancer Screening Robert Smith, PhD, and his colleagues say that standardizing mammography data shows regular mammograms do save lives from breast cancer. Read more here.

Study mentioned: Duffy SW, et al. Real and artificial controversies in breast cancer screening. Breast Cancer Management. November 2013.

Post-Authorization Activity Table (PAAT) for Stivarga

The PAAT describes post-authorization activity for Stivarga, a product which contains the medicinal ingredient regorafenib (as regorafenib monohydrate). Based on Health Canada's review, the benefit/risk profile of Stivarga is favourable for the treatment of patients with metastatic colorectal cancer who have been previously treated with fluoropyrimidine-based chemotherapy, oxaliplatin, irinotecan, an anti-vascular endothelial growth factor therapy, and, if KRAS wild type, an anti-epidermal growth factor receptor therapy. Read more here.

Tuesday 10 December 2013

Bigger breasts, lack of exercise tied to breast cancer mortality

If a woman develops breast cancer, having larger breasts and being sedentary might increase her risk of dying from the disease, a large, long-term study suggests. The new study looked at how both exercise and breast size might predict survival if breast cancer does develop, said study researcher Paul Williams, a staff scientist at the Lawrence Berkeley National Laboratory, in Berkeley, Calif. Read more here.

Study mentioned: Williams PT (2013) Breast Cancer Mortality vs. Exercise and Breast Size in Runners and Walkers. PLoS ONE 8(12): e80616.

Many lung cancer tumors may prove harmless

Smokers who have a CT scan to check for lung cancer stand a nearly one-in-five chance that doctors will find and potentially treat a tumor that would not have caused illness or death, researchers report. Despite the finding, major medical groups indicated they are likely to stick by current recommendations that a select segment of long-time smokers undergo regular CT scans. Read more here.

Gene therapy shows promise against leukemia, other blood cancers

Preliminary research shows that gene therapy might one day be a powerful weapon against leukemia and other blood cancers. The experimental treatment coaxed certain blood cells into targeting and destroying cancer cells, according to research presented this weekend at the American Society of Hematology's annual meeting in New Orleans. Read more here.

Type 2 diabetes might raise risk of liver cancer

People with type 2 diabetes might be at somewhat higher risk of developing liver cancer, according to a large, long-term study. The research suggests that those with type 2 diabetes have about two to three times greater risk of developing hepatocellular carcinoma (HCC) -- the most common type of liver cancer -- compared to those without diabetes. The new research is scheduled for presentation at an American Association for Cancer Research meeting in Atlanta. Read more here.

Germs that inhabit gut may affect colon cancer risk

Researchers analyzed DNA in fecal samples collected from 47 colorectal cancer patients and 94 people without the disease to determine the level of diversity of their gut bacteria. Study authors led by Jiyoung Ahn, at the New York University School of Medicine, concluded that decreased bacterial diversity in the gut was associated with colorectal cancer. Read more here.

Study mentioned: Ahn J, et al. Human Gut Microbiome and Risk of Colorectal Cancer. J Natl Cancer Inst. 2013 Dec 6. [Epub ahead of print] PMID: 24316595

Men who smoke after cancer diagnosis face higher death risk

Men who keep smoking after being diagnosed with cancer are more likely to die than those who quit smoking, a new study shows. The findings demonstrate that it's not too late to stop smoking after being diagnosed with cancer, researchers say. Read more here.

Study mentioned: Tao L, et al. Impact of Postdiagnosis Smoking on Long-term Survival of Cancer Patients: The Shanghai Cohort Study. Cancer Epidemiol Biomarkers Prev. 2013 Dec;22(12):2404-11. PMID: 24319070

Some diabetes drugs may affect cancer risk in women

A certain type of diabetes drug may lower cancer risk in women with type 2 diabetes by up to one-third, while another type may increase the risk, according to a new study. Cleveland Clinic researchers analyzed data from more than 25,600 women and men with type 2 diabetes to compare how two groups of widely used diabetes drugs affected cancer risk. Read more here.

Study mentioned: Sun GEC, et al. Gender-specific effects of oral hypoglycaemic agents on cancer risk in type 2 diabetes mellitus. Diabetes, Obesity and Metabolism. Article first published online: 5 Dec 2013.

New test may help predict survival from ovarian cancer

By counting the number of cancer-fighting immune cells inside tumors, scientists say they may have found a way to predict survival from ovarian cancer. The researchers developed an experimental method to count these cells, called tumor-infiltrating T lymphocytes, in women with early stage and advanced ovarian cancer. Read more here.

Study mentioned: Robins HS, et al. Digital genomic quantification of tumor-infiltrating lymphocytes. Sci Transl Med. 2013 Dec 4;5(214):214ra169. PMID: 24307693

Pollen allergies may raise risk for blood cancers in women

Women with pollen allergies may be at increased risk for blood cancers such as leukemia and lymphoma, a new study suggests. Researchers did not uncover the same link in men. This suggests there is something unique in women that causes chronic allergy-related stimulation of the immune system to increase vulnerability to the development of blood cancers, the study authors said. Read more here.

Study mentioned: Shadman M, et al. Associations between allergies and risk of hematologic malignancies: Results from the VITamins and lifestyle cohort study. Am J Hematol. 2013 Dec;88(12):1050-4. PMID: 23918679

Frequent mammograms tied to lower risk of breast cancer spread

Breast cancer patients who have mammograms every 12 to 18 months have less chance of lymph node involvement than those who wait longer, therefore improving their outlook, according to an early new study. "We found doing mammograms at intervals longer than one and a half years essentially does affect patient prognosis," said study researcher Dr. Lilian Wang. "In our study, those patients were found to have a significantly greater lymph node positivity." Wang, an assistant professor of radiology at Northwestern University's Feinberg School of Medicine, is scheduled to present the findings Wednesday at the annual meeting of the Radiological Society of North America, in Chicago. Read more here.

Cancer mutation likely trigger of scleroderma

Johns Hopkins scientists have found evidence that cancer triggers the autoimmune disease scleroderma, which causes thickening and hardening of the skin and widespread organ damage. A report on the discovery also suggests that a normal immune system is critical for preventing the development of common types of cancer. Read more here.

Study mentioned: Joseph CG et al. Association of the Autoimmune Disease Scleroderma with an Immunologic Response to Cancer. Science. Published Online December 5 2013.

Unlocking how brain cancer cells hide from drugs

Researchers from UCLA’s Jonsson Comprehensive Cancer Center have discovered a biological mechanism that allows brain tumor cells to escape from the drugs designed to target them, resulting in drug resistance. The JCCC team, led by first author David Nathanson, assistant professor of Molecular and Medical Pharmacology, and former UCLA professor Paul Mischel, now at the Ludwig Institute for Cancer Research at UCSD, found that the tumor cells are able to eliminate the gene mutation, essentially removing the target while the drug is present and allowing the tumor to become drug resistant. Read more here.

Study mentioned: Nathanson DA, et al. Targeted Therapy Resistance Mediated by Dynamic Regulation of Extrachromosomal Mutant EGFR DNA. Science. 2013 Dec 5. [Epub ahead of print] PMID: 24310612

Learning from the FDA breakthrough therapies pathway

The expedited USA Food and Drug Administration regulatory pathway for 'breakthrough therapies' has already yielded its first two approvals and more than 26 designations, for 30 candidates in 22 indications. Less than a year on, on 1 November 2013, obinutuzumab became the first drug to graduate from the breakthrough therapy programme into the real world. Weeks later, it was joined by ibrutinib. The breakthrough era has arrived, wrote Asher Mullard in an article published in the Nature Reviews Drug Discovery. Read more here.

Study mentioned: Mullard A. Learning from the 2012-2013 class of breakthrough therapies. Nat Rev Drug Discov. 2013 Nov 29;12(12):891-3. PMID: 24287765

Review calls for increased attention to cancer risk from silica

A new review highlights new developments in understanding the health effects of silica, and calls for action to reduce illness and death from silica exposure at work, including stronger regulations, heightened awareness and prevention, and increased attention to early detection of silicosis and lung cancer using low dose CT scanning. Read more here.

Study mentioned: Steenland K, Ward E. Silica: A lung carcinogen. CA: A Cancer Journal for Clinicians. Article first published online: 10 Dec 2013.

300,000 Americans may reveal cancer prevention clues

The American Cancer Society just finished enrolling more than 300,000 Americans in its Cancer Prevention Study-3 (CPS-3). Cancer-free adults aged 30 to 65 across the United States volunteered by providing a blood sample, having their waist measured, and filling out two questionnaires about a host of topics – from their family history of cancer to personal health habits to what type of work they do. The American Cancer Society will follow the health of these participants over time, monitoring who develops cancer and who doesn’t – with the goal of ultimately discovering more and better ways to prevent cancer. Read more here.

Monday 9 December 2013

Examining the social side effects of brain cancer

Researchers at the Alberta Children’s Hospital are working to help children who survive brain cancer with their social skills as they recover and transition back into their peer groups. Experts say children who survive brain cancer often experience impaired social skills as a side effect of chemotherapy and radiation. Dr. Fiona Schulte is leading a research study to help address what she calls “social deficits”. Read more here.

Call for proposals on translational research on tertiary prevention in cancer patients

The TRANSCAN network has announced its third transnational call to fund multinational research projects under the theme of "Translational research on tertiary prevention in cancer patients"

AIM OF THE CALL

Cancer control aims to reduce incidence, morbidity and mortality of malignancies and to improve the quality of life in cancer patients. Prevention provides the most cost-effective long-term strategies for cancer control, particularly when the related interventions are placed within larger programs oriented towards chronic disease prevention and health promotion. Therefore, the development of novel, highly specific and increasingly effective tools and strategies for the prevention of cancer represents a major challenge for translational cancer research. In particular, reducing the risk of cancer recurrence and ensuring cancer survivors a good quality of life represent goals of utmost importance for patients, health care providers and health care systems in terms of allocations of public funds. Read more here.

Boosting the immune system to treat brain cancer

Researchers at the University of Calgary’s Hotchkiss Brain Institute (HBI) have made a discovery that could lead to better treatment for patients suffering from brain cancer.

Despite current treatment strategies, the median survival for patients with the most aggressive brain cancer – called glioblastoma, is 15 months. Less than five per cent of patients survive beyond five years.

HBI member V. Wee Yong, PhD and research associate Susobhan Sarkar, PhD, and their team including researchers from the Department of Clinical Neurosciences and the university’s Southern Alberta Cancer Research Institute, looked at human brain tumour samples and discovered that specialized immune cells in brain tumour patients are compromised. The researchers took this discovery and, in an animal model, identified a drug that is able to re-activate those immune cells and reduce brain tumour growth, thereby increasing the lifespan of mice two to three times. Their discovery was published December 8 in the prestigious journal Nature Neuroscience. Read more here.

Study mentioned: Sarkar S. et. al. Therapeutic activation of macrophages and microglia to suppress brain tumor-initiating cells. Nature Neuroscience. Epub 2013 Dec 8. doi:10.1038/nn.3597.

Friday 6 December 2013

Navigators help cancer patients manage their care

Receiving support from a patient navigator can make a difference in the way newly diagnosed cancer patients feel about their care. According to a study published in the Journal of Clinical Oncology, patients with a nurse navigator rated their care higher and reported fewer problems than patients without one. The study involved about 500 people in Seattle, Washington, newly diagnosed with breast, lung, colon, or rectal cancer. Read more here.

Study mentioned: Wagner EH, et al. Nurse Navigators in Early Cancer Care: A Randomized, Controlled Trial. J Clin Oncol. 2013 Nov 25. [Epub ahead of print] PMID: 24276777

NIH-funded study shows increased survival in men with metastatic prostate cancer who receive chemotherapy when starting hormone therapy

Men with hormone-sensitive metastatic prostate cancer who received the chemotherapy drug docetaxel given at the start of standard hormone therapy lived longer than patients who received hormone therapy alone, according to early results from a National Institutes of Health-supported randomized controlled clinical trial. Read more here.

Predicting ovarian cancer by counting tumor-attacking immune cells

Scientists at Fred Hutchinson Cancer Research Center have developed a new method for counting a special class of cancer-fighting cells – called tumor-infiltrating T lymphocytes - reliably, quickly and cheaply in patients with early stage and advanced ovarian cancer. Such technology, a DNA - amplification technique, has the potential to predict treatment response, cancer recurrence and disease-free survival earlier and more effectively than any current method, according to lead researcher and cancer geneticist Jason H. Bielas, Ph.D., an associate member of the Human Biology and Public Health Sciences divisions at Fred Hutch. Read more here.

Study mentioned: Robins HS, et al. Digital Genomic Quantification of Tumor-Infiltrating Lymphocytes. Sci Transl Med. 2013; 5(214):p. 214ra169.

3-D mammography increases cancer detection and reduces call-back rates, Penn study finds

Compared to traditional mammography, 3D mammography—known as digital breast tomosynthesis—found 22 percent more breast cancers and led to fewer call backs in a large screening study at the Hospital of the University of Pennsylvania, researchers reported today at the annual meeting of the Radiological Society of North America (RSNA). Read more here.

New drug cuts risk of deadly transplant side effect in half

A new class of drugs reduced the risk of patients contracting a serious and often deadly side effect of lifesaving bone marrow transplant treatments, according to a study from researchers at the University of Michigan Comprehensive Cancer Center. The study combined the drug vorinostat with standard medications given after transplant, resulting in 22 percent of patients developing graft-vs.-host disease compared to 42 percent of patients who typically develop this condition with standard medications alone. Read more here.

Study mentioned: Choi SW, et al. Vorinostat plus tacrolimus and mycophenolate to prevent graft-versus-host disease after related-donor reduced-intensity conditioning allogeneic haemopoietic stem-cell transplantation: a phase 1/2 trial. Lancet Oncol. 2013 Nov 29. [Epub ahead of print] PMID: 24295572

Blocking antioxidants in cancer cells reduces tumor growth in mice

In the Journal of Clinical Investigation, Navdeep Chandel and colleagues from Northwestern University report the effects of a SOD1 pharmacological inhibitor on non-small-cell lung cancer (NSCLC) cells. The inhibitor, called ATN-224, stunted the growth of human NSCLC cells in culture and induced their death. Read more here.

Study mentioned: Glasauer A, et al. Targeting SOD1 reduces experimental non-small-cell lung cancer. J Clin Invest. 2013 Dec 2. [Epub ahead of print] PMID: 24292713

APO-SYS: How modulation of apoptosis can be used in the treatment of cancer and AIDS

The APO-SYS project aimed to understand how apoptosis can be modulated, so that scientists can control which cells live and which undergo programmed cell death, especially in AIDS and cancer. An expert team of researchers from different scientific disciplines allowed partners to integrate their knowledge within a multidisciplinary approach, to build a computational model describing interactions between the components of biological systems. Then, using modern high-throughput experimental techniques the APO-SYS consortium collected quantitative data for validation of the model. This allowed the APO-SYS team to address the question of how modulation of apoptosis can be used in the treatment of cancer and AIDS. Read more here.

Wednesday 4 December 2013

Predicting outcome for high-dose IL-2 therapy in cancer patients

Lazlo Radvanyi and colleagues at M.D. Anderson Cancer Center performed an in depth analysis of Treg populations in melanoma patients undergoing HD IL-2 therapy. The authors identified a distinct population of Treg cells that expressed the inducible T cell costimulator (ICOS) that was highly proliferative following the first cycle of HD IL-2. Read more here.

Study mentioned: Sim GC, et al. IL-2 therapy promotes suppressive ICOS+ Treg expansion in melanoma patients. J Clin Invest. 2013 Dec 2. pii: 46266. [Epub ahead of print] PMID: 24292706

Onartuzumab in combination with erlotinib in patients with advanced NSCLC

In a randomised, phase II study in patients with recurrent non-small cell lung cancer, onartuzumab plus erlotinib was associated with improved progression-free survival and overall survival in the MET-positive population. These results combined with the worse outcomes observed in MET-negative patients treated with onartuzumab highlight the importance of diagnostic testing in drug development, according to conclusion of the article published by Dr David Spigel of the Sarah Cannon Research Institute, Nashville, USA and colleagues. Read more here.

Study mentioned: Spigel DR, et al. Randomized Phase II Trial of Onartuzumab in Combination With Erlotinib in Patients With Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2013 Nov 10;31(32):4105-14. PMID: 24101053

Summary Basis of Decision (SBD) for Istodax

Health Canada has issued a Notice of Compliance under the Notice of Compliance with Conditions Guidance to Celgene Inc. for the Istodax drug product. Based on Health Canada's review, the benefit/risk profile of Istodax is favourable for the treatment of patients with relapsed/refractory peripheral T-cell lymphoma who are not eligible for transplant and have received at least one prior systemic therapy. Read more here.

Tuesday 3 December 2013

Xeloda (capecitabine) - Risk of severe skin reactions

Hoffmann-La Roche Limited (Roche), in consultation with Health Canada, would like to inform you of the risk of severe cutaneous reactions associated with the use of Xeloda. XELODA is authorized for the following indications: 1. Colorectal cancer: Adjuvant treatment of patients with stage III (Dukes’ stage C) colon cancer; first-line treatment of patients with metastatic colorectal cancer; treatment of metastatic colorectal cancer, in combination with oxaliplatin, following failure of irinotecan-containing combination chemotherapy; 2. Breast cancer: Treatment of patients with advanced or metastatic breast cancer, in combination with docetaxel, after failure of prior anthracycline containing chemotherapy; treatment of advanced or metastatic breast cancer after failure of standard therapy including a taxane, unless therapy with a taxane is clinically contraindicated. Read more here.

IMI 11th call for proposals: blood-based biomarker assays for personalised tumour therapy

The Innovative Medicines Initiative (IMI) will launch its 11th Call for Proposals in December 2013. The indicative topics include a 5 year project on "Blood-based biomarker assays for personalized tumour therapy: value of latest circulating biomarkers." Read more here.

Monday 2 December 2013

Post-Authorization Activity Table (PAAT) for adcetris

The PAAT describes post-authorization activity for Adcetris, a product which contains the medicinal ingredient brentuximab vedotin. Based on Health Canada's review, the benefit/risk profile of Adcetris is favourable for: 1. The treatment of patients with Hodgkin lymphoma (HL) after failure of autologous stem cell transplant (ASCT) or after failure of at least two multi-agent chemotherapy regimens in patients who are not ASCT candidates; 2. The treatment of patients with systemic anaplastic large cell lymphoma (sALCL) after failure of at least one multi-agent chemotherapy regimen. Read more here.

Cyclin D1 governs microRNA processing in breast cancer

Cyclin D1, a protein that helps push a replicating cell through the cell cycle also mediates the processing and generation of mature microRNA (miRNA), according to new research. The research suggests that a protein strongly implicated in human cancer also governs the non-protein-coding genome. The non-coding genome, previously referred to as junk DNA, makes up most of the human genome, and unlike the coding genome, varies greatly between species. Read more here.

Study mentioned: Yu Z, et al. Cyclin D1 induction of Dicer governs microRNA processing and expression in breast cancer. Nat Commun. 2013 Nov 29;4:2812. PMID: 24287487

Scientists discover how thalidomide-like drugs fight cancer

Despite its tragic legacy of causing birth defects 50 years ago, thalidomide — and newer drugs derived from it — has been reborn as an effective treatment for multiple myeloma and other cancers. How they act to slow cancer's spread, however, has long defied explanation. In a new report, scientists at Dana-Farber Cancer Institute say they have discovered that the drugs kill multiple myeloma cells by a mechanism that's different from the way that they cause birth defects. Read more here.

Study mentioned: Lu G, et al. The Myeloma Drug Lenalidomide Promotes the Cereblon-Dependent Destruction of Ikaros Proteins. Science. Published Online November 29 2013.

Exome sequencing identifies frequent inactivating mutations in intrahepatic cholangiocarcinomas

Exome sequencing of 32 intrahepatic cholangiocarcinomas has revealed recurrent inactivating mutations in several genes involved in chromatin remodelling that were previously unknown in this type of cancer. The study also identified frequent mutations at previously reported hotspots in the genes encoding metabolic enzymes. Read more here.

Study mentioned: Jiao Y, et al. Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas. Nat Genet. 2013 Dec;45(12):1470-3. PMID: 24185509

Friday 29 November 2013

European Medicines Agency recommends changes in use of ponatinib in order to minimise risk of thrombosis

The European Medicines Agency’s Committee for Medicinal Products for Human Use has made a number of recommendations to help minimise the risk of thrombs obstructing arteries or veins in patients taking the leukaemia medicine ponatinib (Iclusig). Recommendations follow a review of updated clinical trial data indicating that thrombosis was occurring at a higher rate than was observed at the time of the ponatinib’s initial authorisation. Read more here.

Thursday 28 November 2013

Using microRNA fit to a T (cell)

Researchers at the University of California, San Diego School of Medicine have successfully targeted T lymphocytes – which play a central role in the body’s immune response – with another type of white blood cell engineered to synthesize and deliver bits of non-coding RNA or microRNA (miRNA). The achievement in mice studies may be the first step toward using genetically modified miRNA for therapeutic purposes, perhaps most notably in vaccines and cancer treatments, said principal investigator Maurizio Zanetti, MD, professor in the Department of Medicine and director of the Laboratory of Immunology at UC San Diego Moores Cancer Center. Read more here.

Study mentioned: Almanza G, et al. Synthesis and delivery of short, noncoding RNA by B lymphocytes. PNAS. Published online before print November 25, 2013.

Cancer researchers translate new laboratory findings to enhance melanoma treatment

Translational researchers from UCLA’s Jonsson Comprehensive Cancer Center have published results of two back-to-back studies in the journal Cancer Discovery that provide critical insights into two key areas of how tumors resist BRAF inhibitors: the key cell-signaling pathways BRAF-mutant melanoma cells use to learn how to become resistant to inhibitor drugs, and how the limited focus of BRAF inhibitors allows melanoma cells to evolve and develop drug resistance. Read more here.

Study mentioned: Shi H, et al. Acquired Resistance and Clonal Evolution in Melanoma during BRAF Inhibitor Therapy. Cancer Discov. 2013 Nov 21. [Epub ahead of print] PMID: 24265155

Study mentioned: Shi H, et al. A Novel AKT1 Mutant Amplifies an Adaptive Melanoma Response to BRAF Inhibition. Cancer Discov. 2013 Nov 21. [Epub ahead of print] PMID: 24265152

Two human proteins found to affect how "jumping gene" gets around

Using a new method to catch elusive “jumping genes” in the act, researchers have found two human proteins that are used by one type of DNA to replicate itself and move from place to place. The discovery breaks new ground, they say, in understanding the arms race between a jumping gene driven to colonize new areas of the human genome and cells working to limit the risk posed by such volatile bits of DNA. Read more here.

Study mentioned: Taylor MS, et al. Affinity Proteomics Reveals Human Host Factors Implicated in Discrete Stages of LINE-1 Retrotransposition. Cell. 2013 Nov 21;155(5):1034-48. PMID: 24267889

Targets of anticancer drugs have broader functions than what their name suggests

Drugs that inhibit the activity of enzymes called histone deacetylases (HDACs) are being widely developed for treating cancer and other diseases, with two already on the market. Researchers at the Perelman School of Medicine, University of Pennsylvania, show that a major HDAC still functions in mice even when its enzyme activity is abolished, suggesting that the beneficial effects of HDAC inhibitors may not actually be through inhibiting HDAC activity, and thus warranting the reassessment of the molecular targets of this class of drugs. Read more here.

Study mentioned: Sun Z, et al. Deacetylase-Independent Function of HDAC3 in Transcription and Metabolism Requires Nuclear Receptor Corepressor. Mol Cell. 2013 Nov 19. pii: S1097-2765(13)00788-0. [Epub ahead of print] PMID: 24268577

UCLA researchers' new technique improves accuracy, ease of cancer diagnosis

A team of researchers from UCLA and Harvard University have demonstrated a technique that, by measuring the physical properties of individual cells in body fluids, can diagnose cancer with a high degree of accuracy. The technique, which uses a deformability cytometer to analyze individual cells, could reduce the need for more cumbersome diagnostic procedures and the associated costs, while improving accuracy over current methods. Read more here.

Study mentioned: Tse HT, et al. Quantitative diagnosis of malignant pleural effusions by single-cell mechanophenotyping. Sci Transl Med. 2013 Nov 20;5(212):212ra163. PMID: 24259051

European Medicines Agency recommends refusal of the marketing authorisation for masitinib

The European Medicines Agency Committee for Medicinal Products for Human Use (CHMP) has adopted a negative opinion, recommending the refusal of the marketing authorisation for the medicinal product masitinib (Masican), intended for the treatment of malignant gastrointestinal stromal tumour (GIST). Read more here.

European Medicines Agency recommends extension of indications for paclitaxel protein-bound particles for injectable suspension (albumin-bound)

The European Medicines Agency Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending a variation to the terms of the marketing authorisation for the medicinal product Abraxane. The CHMP adopted a new indication as follows: "Abraxane in combination with gemcitabine is indicated for the first-line treatment of adult patients with metastatic adenocarcinoma of the pancreas". Read more here.

European Medicines Agency issues positive recommendation on generic zoledronic acid

The European Medicines Agency Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion, recommending the granting of a marketing authorisation for the medicinal product Zoledronic Acid Accord 4mg/5ml concentrate for solution for infusion intended for the prevention of skeletal related events (pathological fractures, spinal compression, radiation or surgery to bone, or tumour-induced hypercalcaemia) in adult patients with advanced malignancies involving bone, and the treatment of tumour-induced hypercalcaemia (TIH). Read more here.

Eating nuts may lower pancreatic cancer risk

In a recent study, researchers analyzed data on 75,680 women from the Nurses' Health study to assess the potential association between nut consumption and the risk for pancreatic cancer. After adjusting the data for various risk factors such as smoking, age and physical activity, the researchers found that women who ate at least one ounce of nuts twice weekly had a 35 percent significantly reduced risk of pancreatic cancer when compared to those who principally did not eat nuts. Read more here.

Study mentioned: Bao Y, et al. Nut consumption and risk of pancreatic cancer in women. Br J Cancer. 2013 Nov 26;109(11):2911-6. Epub 2013 Oct 22. PMID: 24149179

Researchers receive Movember Discovery Grant: Findings could lead to new diagnostic tool

Prostate cancer is the most common type of cancer in Canadian men, but some men may have a type of the disease that doesn't require aggressive treatment.

As part of a Movember Discovery Grant from Prostate Cancer Canada, University of Calgary researchers are trying to understand indolent (dormant) prostate cancer better, in hopes of developing a test to differentiate dormant versus aggressive disease upon initial diagnosis. Dormant prostate cancer is not aggressive and does not spread, thereby making it less of an immediate threat than aggressive prostate cancer. Read more here.

Wednesday 27 November 2013

Seven key findings from 8-year study of cancer caregivers

To better understand the effects of cancer on the quality of life of caregivers, the American Cancer Society’s Behavioral Research Center conducted an 8-year study – the American Cancer Society National Quality of Life Survey for Caregivers – initiated in 2002. It is the largest nationwide, long-term study of its kind, encompassing surveys of nearly 2,000 cancer caregivers. Read more here.

Tuesday 26 November 2013

FDA approves Nexavar for advanced thyroid cancer

The US Food and Drug Administration (FDA) has approved Nexavar (sorafenib) to treat some people with advanced thyroid cancer. The drug was already on the market for treating some types of kidney cancer and liver cancer. The new approval is for treating differentiated thyroid cancer – the most common type – that has come back after treatment or that has spread to other parts of the body (metastasized), and is no longer responding to radioactive iodine treatment. Read more here.

The international pooling project of mammographic density

The International Pooling Project of Mammographic Density will create the first standardized pooled data/imaging resource, which will include women from more than 20 countries worldwide, spanning low- to high-incidence countries. It will be used to describe and account for international variations in mammographic density and investigate to what extent they contribute to international variations in breast cancer incidence rates. After the first year of fieldwork for the study, participating studies have now been identified, and anonymized images and data are being assembled at IARC. Read more here.

IARC Monographs Volumes 1 to 42 now freely available on-line

We are pleased to announce that IARC Monographs Volumes 1 to 42 are now available on-line in PDF format. This huge body of work, previously available only in print, represents all evaluations made by IARC Monographs Working Groups between 1972 and 1987. Access the monographs here.

Monday 25 November 2013

NIH mouse study finds gut microorganisms may determine cancer treatment outcome

An intact population of microorganisms that derive food and benefit from other organisms living in the intestine is required for optimal response to cancer therapy, according to a mouse study by scientists at the National Cancer Institute, part of the National Institutes of Health, and their collaborators. Read more here.

Study mentioned: Iida N, et al. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science. 2013 Nov 22;342(6161):967-70. PMID: 24264989

Drug strategy blocks a leader driver of cancer

Using a new strategy, UC San Francisco researchers have succeeded in making small molecules that irreversibly target a mutant form of protein, called ras, without binding to the normal form. This feature distinguishes the molecules from all other targeted drug treatments in cancer, according to the researchers. Read more here.

Study mentioned: Ostrem JM, et al. K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions. Nature. 2013 Nov 20. [Epub ahead of print] PMID: 24256730

Worldwide trends show oropharyngeal cancer rates increasing

NCI scientists report that the incidence of oropharyngeal cancer significantly increased during the period 1983-2002 among people in countries that are economically developed. The results of this study, by Anil K. Chaturvedi, Ph.D., Division of Cancer Epidemiology and Genetics, NCI, and his colleagues, appeared online in the Journal of Clinical Oncology. Read more here.

Study mentioned: Chaturvedi AK, et al. Worldwide Trends in Incidence Rates for Oral Cavity and Oropharyngeal Cancers. J Clin Oncol. 2013 Nov 18. [Epub ahead of print] PMID: 24248688

Oral drug may improve survival in men with metastatic prostate cancer

An investigational prostate cancer treatment slows the disease’s progression and may increase survival, especially among men whose cancer has spread to the bones, according an analysis led by the Duke Cancer Institute. The study adds long-term survival and safety data for the drug tasquinimod, a new candidate for treating advanced and recurrent prostate cancer. Read more here.

Study mentioned: Armstrong AJ, et al. Long-term Survival and Biomarker Correlates of Tasquinimod Efficacy in a Multicenter Randomized Study of Men with Minimally Symptomatic Metastatic Castration-Resistant Prostate Cancer. Clin Cancer Res. 2013 Nov 19. [Epub ahead of print] PMID: 24255071

European Medicines Agency recommends change in indication for cetuximab to RAS wild-type metastatic colorectal cancer

The European Medicines Agency Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending a variation to the terms of the marketing authorisation for the medicinal product cetuximab (Erbitux). The CHMP changed the indication for use in metastatic colorectal cancer to clarify the particular genetic makeup of the cancer that must be present before treatment with Erbitux, which is described as epidermal growth factor receptor (EGFR)-expressing, RAS wild-type disease. Read more here.

Smartphone smoking cessation apps need an upgrade

Smokers are increasingly turning to smartphone apps to help them quit. But many of these apps fail to incorporate proven quit-smoking practices, according to an analysis of the 98 most popular iPhone and Android smoking cessation apps. The American Cancer Society and George Washington University researchers identified the most popular apps as of February 2012 for the study. Read more here.

Study mentioned: Abroms LC, et al. A content analysis of popular smartphone apps for smoking cessation. Am J Prev Med. 2013 Dec;45(6):732-6. PMID: 24237915

Friday 22 November 2013

Ontario’s successes in pathology reporting have potential to improve practice across Canada

As is your pathology, so is your medicine.

So said Dr. William Osler, a Canadian physician and one of the founding fathers of modern medicine. He was referring to the critical role that pathology – the study of tissue samples to diagnose disease – plays in diagnosing cancer and identifying treatment options.

Almost 100 years later, we’ve made tremendous progress in diagnosing and treating cancer, and there continue to be opportunities to improve. A recent article in the Journal of Oncology Practice has showcased the advancement of pathology reporting in Ontario. Initiated in 2008, Cancer Care Ontario’s Pathology Reporting Project uses structured electronic checklists to make the reporting of diagnostic findings by pathologists more complete. This has resulted in the vast majority of Ontario hospitals implementing electronic tools to report cancer diagnosis, standardized reporting and more complete pathology reports. This leads to more effective care planning and better outcomes for patients. Read more here.

Study mentioned: Srigley J, et al. Closing the quality loop: facilitating improvement in oncology practice through timely access to clinical performance indicators. J Oncol Pract. 2013 Sep 1;9(5):e255-61. doi: 10.1200/JOP.2012.000818. Epub 2013 Jul 2. PubMed PMID: 23943888.

Lung cancer kills more women in Canada than in other OECD countries

In Canada, 47 out of 100,000 women die of lung cancer every year—almost double the average rate of 26.5 per 100,000 among member countries of the Organisation for Economic Co-operation and Development (OECD).

A new report by the Canadian Institute for Health Information (CIHI) notes that this may be related to the fact that the percentage of Canadian women who smoked in the 1980s was more than double that of today, and a lag time of up to 30 years exists between a reduction in smoking rates and a decline in lung cancer rates. Read more here.

Thursday 21 November 2013

Study ties nuts to a lower risk of death, including from heart disease or cancer

Researchers tracked 119,000 men and women and found that those who ate nuts roughly every day were 20 per cent less likely to die during the study period than those who never ate nuts. Eating nuts less often also appeared to lower the death risk, in direct proportion to consumption. The risk of dying of heart disease dropped 29 per cent and the risk of dying of cancer fell 11 per cent among those who had nuts seven or more times a week compared with people who never ate them. Read more here.

Study mentioned: Bao Y, et al. Association of Nut Consumption with Total and Cause-Specific Mortality. N Engl J Med 2013; 369:2001-2011.

Cancer patients prefer healthy meals to greasy foods, study finds

A study released by the Cancer Nutrition Consortium aims to improve the lives of cancer patients by helping them get the meals they want while combatting the weight loss and fatigue that often comes with aggressive treatment. Researchers surveyed 1,203 patients at seven of the world’s leading cancer centres, including Dana-Farber and the Mayo Clinic, and found that 40 per cent developed more sensitive palates after starting treatments like chemotherapy and radiation. Read more here.

Read the full report here.

Wednesday 20 November 2013

More blood clots in chemotherapy patients, researchers say

Blood clots may be more prevalent in patients undergoing chemotherapy than previously thought, according to new research from Duke University and King’s College Hospital, London. Lung, pancreatic and stomach cancers were associated with the highest incidences of venous thromboembolism (VTE). Read more here.

Study mentioned: Lyman GH, et al. Venous Thromboembolism Risk in Patients With Cancer Receiving Chemotherapy: A Real-World Analysis. Oncologist. 2013 Nov 8. [Epub ahead of print] PMID: 24212499

FIRE-e: kindling for a CRC practice change?

In this short Medscape video, David Kerr, Professor of Cancer Medicine at the University of Oxford, United Kingdom, and past President of ESMO, discusses the updated results of the FIRE-3 study, which were presented recently by the German/Austrian group at the 2013 European Cancer Congress. This is a front-line, randomized study comparing FOLFIRI plus bevacizumab vs FOLFIRI plus cetuximab. View the video here.

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Screening Programme for Efficient Clinical Trial Access – lung cancer biomarker screening platform

The European Organisation for Research and Treatment of Cancer has announced that it will build a Screening Programme for Efficient Clinical Trial Access (SPECTA) for patients with lung cancer. This programme, SPECTAlung, will prospectively collect biological materials from patients who have been diagnosed with lung cancer, starting with non-small cell lung cancer and enable efficient clinical trial access for these patients. Read more here.

Clinical predictors of acute urinary symptoms after radiotherapy for prostate cancer

An interim study by Italian researchers showed that using a modelling programme together with IPSS questionnaire and dosage measure can predict the severity of acute urinary symptoms in patients with early prostate cancer who underwent radiotherapy. The findings were presented by Dr Cesare Cozzarini of the San Raffaele Scientific Institute, Milan, Italy at the 5th European Multidisciplinary Meeting on Urological Cancers (EMUC) held in Marseille, France (15-17 November 2013). Read more here.

Obesity found to be major risk factor in developing basal-like breast cancer

Using a mouse model developed to study the basal-like subtype of breast cancer, a team led by Liza Makowski, assistant professor in the Department of Nutrition with the UNC Gillings School of Global Public Health and member of the UNC Lineberger Comprehensive Cancer Center, and Sneha Sundaram, PhD, a post-doctoral fellow in the Makowski Lab, discovered that obesity radically alters the cellular microenvironment of mammary glands in ways favorable to the growth of basal-like tumors. One major change is that obesity promotes a growth factor signaling pathway between the hepatocyte growth factor (HGF) protein and an oncogene known as c-Met that is linked with basal-like cancer formation. In animals with elevated levels of HGF, the development of basal-like tumors increased. Read more here.

Study mentioned: Sundaram S, et al. Role of HGF in obesity-associated tumorigenesis: C3(1)-TAg mice as a model for human basal-like breast cancer. Breast Cancer Res Treat. 2013 Nov 12. [Epub ahead of print] PMID: 24218051

POEM of the week podcast: Finasteride prevents low-grade prostate cancers, but does not reduce mortality

Dr. Ebell and Dr. Wilkes discuss the POEM titled "Finasteride prevents low-grade prostate cancers, but does not reduce mortality" Download podcast here.

Kids' Cancer Treatments May Cause Heart Trouble

A new study conducted at the University of Minnesota indicates that doctors should be monitoring young child cancer patients for heart disease risk factors. According to the study, conducted on more than 300 boys and girls ages 9-18, "childhood leukemia survivors had a 9% decrease in arterial health after completing chemotherapy." With the five-year survival rate for childhood cancers in the U.S. currently around 83%, the findings from this study indicate that lifestyle changes aimed at lowering cardiovascular risk in childhood cancer survivors are necessary. To read more about this study, presented on November 17, 2013 at the annual meeting of the American Heart Association in Dallas, click here

Tuesday 19 November 2013

Low-intensity therapy very effective in Burkitt lymphoma

For patients with Burkitt's lymphoma, a low-intensity treatment consisting of infused etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab (EPOCH-R) is highly effective, according to a study published in the Nov. 13 issue of the New England Journal of Medicine. Read more here.

Study mentioned: Dunleavy K, et al. Low-intensity therapy in adults with Burkitt's lymphoma. N Engl J Med. 2013 Nov 14;369(20):1915-25. PMID: 24224624

New research shows tea may help slow progression of prostate cancer

The December 2013 issue of the American Journal of Clinical Nutrition features 12 new articles about the relationship between tea and human health. Each paper is based on presentations from world-renowned scientists who participated in the Fifth International Scientific Symposium on Tea and Human Health, held at USDA in September 2012. Highlights of some of the compelling reports published through the AJCN include the following papers. Read more here.

Yuan JM. Cancer prevention by green tea: evidence from epidemiologic studies. Am J Clin Nutr. 2013 Oct 30. [Epub ahead of print] PMID: 24172305

Lambert JD. Does tea prevent cancer? Evidence from laboratory and human intervention studies. Am J Clin Nutr. 2013 Oct 30. [Epub ahead of print] PMID: 24172300

Qigong fights fatigue in prostate cancer survivors

Because cancer patients are often advised to participate in physical activity as a nonpharmacologic way to manage cancer-related fatigue and levels of distress, this trial study was launched to determine if the mind-body activity Qigong holds any promise for older cancer survivors in this regard. The study took place at the Huntsman Cancer Institute at the University of Utah, and it was led by Anita Y. Kinney, MSN, PhD, of the University of New Mexico Cancer Center in Albuquerque and by Rebecca Campo, PhD, of the University of North Carolina at Chapel Hill. Read more here.

Study mentioned: Campo RA, et al. Levels of fatigue and distress in senior prostate cancer survivors enrolled in a 12-week randomized controlled trial of Qigong. J Cancer Surviv. 2013 Oct 30. [Epub ahead of print] PMID: 24170679

Monday 18 November 2013

E-cigarettes, hookahs gain popularity among US youth

Middle and high school students in the United States are using more non-conventional tobacco products, including electronic cigarettes and hookahs. At the same time they are not significantly decreasing their use of cigarettes, according to the Centers for Disease Control and Prevention (CDC). Read more here.

Study mentioned: Centers for Disease Control and Prevention (CDC). Tobacco product use among middle and high school students - United States, 2011 and 2012. MMWR Morb Mortal Wkly Rep. 2013 Nov 15;62(45):893-7. PMID: 24226625

Researchers work to improve outcomes of lymphoma patients

Researchers at UNMC have discovered that patients with diffuse large B-cell lymphoma don't respond well to the standard drug therapy used to treat this type of cancer if they have high levels of a gene called STAT3. "These results are significant in that it gives oncologists a better understanding of the best way to personalize medical treatment for these patients and offer them hope for more positive outcomes," said Kai Fu, M.D., associate professor in the department of pathology and microbiology. Read more here.

Study mentioned: Huang X, et al. Activation of the STAT3 Signaling Pathway Is Associated With Poor Survival in Diffuse Large B-Cell Lymphoma Treated With R-CHOP. J Clin Oncol. 2013 Nov 12. [Epub ahead of print] PMID: 24220556

How a common chemo drug thwarts graft rejection in bone marrow transplants

Results of a Johns Hopkins study may explain why a chemotherapy drug called cyclophosphamide prevents graft-versus-host (GVHD) disease in people who receive bone marrow transplants. The experiments point to an immune system cell that evades the toxic effects of cyclophosphamide and protects patients from a lethal form of GVHD. The findings could pave the way for improvements in preventing GVHD and rejection of transplanted bone marrow and new therapies to prevent or treat a relapse of the underlying cancer after a transplant. Read more here.

Study mentioned: Kanakry CG, et al. Aldehyde dehydrogenase expression drives human regulatory T cell resistance to posttransplantation cyclophosphamide. Sci Transl Med. 2013 Nov 13;5(211):211ra157. PMID: 24225944

Deletion of any single gene provokes mutations elsewhere in the genome

Johns Hopkins researchers report that the deletion of any single gene in yeast cells puts pressure on the organism’s genome to compensate, leading to a mutation in another gene. Their discovery, which is likely applicable to human genetics because of the way DNA is conserved across species, could have significant consequences for the way genetic analysis is done in cancer and other areas of research, they say. Read more here.

Study mentioned: Teng X, et al. Genome-wide Consequences of Deleting Any Single Gene. Mol Cell. 2013 Nov 6. [Epub ahead of print] PMID: 24211263

Friday 15 November 2013

Prevention Policies Directory supports change at the local level to improve the lives of Canadians

More than one in three Canadians will be diagnosed with cancer in their lifetime. Yet the World Cancer Research Fund estimates that a full third of cancer cases can be prevented by eliminating tobacco use, and another third avoided by a combination of eating nutritious food, limiting alcohol consumption, participating in regular physical activity and maintaining a healthy body weight.

While Canadians can take steps on their own to try to prevent these cancers, healthy public policies such as banning smoking on all city property or keeping junk food out of public buildings are just a few ways local governments can influence the health of residents directly, and help to reduce their risk of getting cancer. Read more here.

Lung cancer top killer, but research dollars and donor support poor: oncologist

Lung cancer kills more Canadians each year than any other malignancy, but the disease receives a disproportionate amount of research and donation dollars compared with far less deadly cancers, says a national advocacy organization. Lung Cancer Canada says the disease causes more than 28 per cent of Canadian cancer deaths -- more than those from breast, colon and prostate cancer combined -- but receives only seven per cent of cancer-specific research funding and 0.1 per cent of charitable cancer donations. Read more here.

Thursday 14 November 2013

FDA approves ibrutinib for mantle cell lymphoma

The US Food and Drug Administration (FDA) has approved ibrutinib (Imbruvica) to treat some people with mantle cell lymphoma. The drug is intended for patients who have stopped responding to treatment, or whose cancer has come back after treatment. Ibrutinib was granted “breakthrough therapy” status, which qualified it for faster FDA review. “Imbruvica’s approval demonstrates the FDA’s commitment to making treatments available to patients with rare diseases,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, in a statement. Read more here.

Report forecasts worsening smoking epidemic in Africa

Africa is poised to become the “future epicenter of the tobacco epidemic,” according to a new analysis from the American Cancer Society. It warns that the number of adults in Africa who smoke could increase to 572 million by 2100, from 77 million today, unless leaders take steps to curb current trends. “The cost of having to intervene in the future rather than preventing it now will be massive,” says Evan Blecher, Ph.D., one the report’s authors and an economist with the International Tobacco Control Research program at the American Cancer Society. Read more here.

Read the full report, Tobacco use in Africa: tobacco control through prevention, here.

Study finds hormonal levels affect endometrial cancer drug efficiency

Modulating the hormonal environment in which endometrial cancers grow could make tumors significantly more sensitive to a new class of drugs known as PARP inhibitors, a researcher at UCLA’s Jonsson Comprehensive Cancer Center has shown for the first time. The findings could lead to a novel one-two punch therapy to fight endometrial cancers and provide an alternative option for conventional treatments that, particularly in advanced disease, have limited efficacy. Read more here.

Study mentioned: Janzen DM, et al. Low Levels of Circulating Estrogen Sensitize PTEN-null Endometrial Tumors to PARP Inhibition In Vivo. Mol Cancer Ther. 2013 Nov 12. [Epub ahead of print] PMID: 24222661

Combination therapy not necessary to achieve remission in breast cancer patients with HER-2-positive disease

Giving trastuzumab and anthracyclines at the same time is effective at treating HER-2-positive breast cancer, but there is concern that this combination can be associated with an increased risk of cardiac toxicity. New research from Aman Buzdar M.D., professor and vice president of clinical research at The University of Texas MD Anderson Cancer Center, and colleagues in the Alliance for Clinical Trials in Oncology, shows these agents do not need to be given concurrently to achieve a high rate of complete pathological remission. Read more here.

Study mentioned: Buzdar AU, et al. Fluorouracil, epirubicin, and cyclophosphamide (FEC-75) followed by paclitaxel plus trastuzumab versus paclitaxel plus trastuzumab followed by FEC-75 plus trastuzumab as neoadjuvant treatment for patients with HER2-positive breast cancer (Z1041): a randomised, controlled, phase 3 trial. The Lancet Oncology, Early Online Publication, 13 November 2013.

NIH study finds low-intensity therapy for Burkitt lymphoma is highly effective

Adult patients with a type of cancer known as Burkitt lymphoma had excellent long-term survival rates—upwards of 90 percent—following treatment with low-intensity chemotherapy regimens, according to a new clinical trial finding. Wyndham H. Wilson M.D. Ph.D., head of NCI’s Lymphoma Therapeutics Section, and colleagues conducted the trial at NIH’s Clinical Center. Read more here.

Study mentioned: Dunleavy K, et al. Low-Intensity Therapy in Adult Burkitt Lymphoma. N Engl J Med 2013; 369:1915-1925.

Wednesday 13 November 2013

Compression bandages work as well for lymphedema as daily massage: study

A new study suggests compression bandages work as well as daily massage for the treatment of a complication of breast cancer treatment called lymphedema. Researchers from McMaster University wanted to compare the available treatments -- compression bandages and daily lymphatic drainage massage with trained therapists. They found no difference in the outcomes and they say that should reassure women for whom lymphatic massage is not an option. Read more here.

Study mentioned: Dayes IS, et al. Randomized trial of decongestive lymphatic therapy for the treatment of lymphedema in women with breast cancer. J Clin Oncol. 2013 Oct 20;31(30):3758-63. PMID: 24043733

Whites', blacks' pancreatic cancer death rates diverge

Pancreatic cancer death rates for whites and blacks in the United States are going in two different directions. Rates among whites have been climbing since the late 1990s. The rates for blacks have been falling since peaking in 1989, according to an American Cancer Society analysis published in the Journal of the National Cancer Institute. Read more here.

Study mentioned: Ma J, et al. Pancreatic Cancer Death Rates by Race Among US Men and Women, 1970-2009. J Natl Cancer Inst. 2013 Nov 7. [Epub ahead of print] PMID: 24203988

Young breast cancer patients with poorer financial status may experience delays in seeking care

Researchers who sought to determine why breast cancers are more deadly in young women found that only a minority of young women experience long delays between the time they detect a breast abnormality and the time they receive a diagnosis, but delays in seeking care are more common in women with fewer financial resources. Read more here.

Study mentioned: Ruddy KJ, et al. Breast cancer presentation and diagnostic delays in young women. Cancer. Article first published online: 11 NOV 2013.

Reclaiming a sex life after prostate cancer

Don Truckey, journalist, screenwriter, and prostate cancer survivor, wrote an e-book called My Prostate Cancer (Sex) Diary: The Story of a Young Survivor Who Didn’t Go Limp, to give comfort and personal information to other prostate-cancer patients and their spouses who likely feel as lost as he did at the time. The Torontonian tells The Globe and Mail that his 50-page story – released appropriately in Movember – is very much a “book of experience … and one I would very much have liked to read.” Read more here.

Canadian Cancer Society: Knowledge to Action grant application forms available

The Canadian Cancer Society is pleased to announce that the online application form is now available for the upcoming Knowledge to Action competition. Please visit the newly redesigned Canadian Cancer Society Research Institute website for application information and research news.

Knowledge to Action Grants: This grant program is designed to support primary knowledge translation (KT) research projects in behavioural and psychosocial sciences that build on existing cancer research findings and aim to improve outcomes and experiences through KT for people and populations at risk, patients, their families and communities across the cancer trajectory. Read more here.

Tuesday 12 November 2013

Common genetic pathway could be conduit to pediatric tumor treatment

Investigators at Johns Hopkins have found a known genetic pathway to be active in many difficult-to-treat pediatric brain tumors called low-grade gliomas, potentially offering a new target for the treatment of these cancers. In laboratory studies, researchers found that the pathway, called mammalian target of rapamycin (mTOR), was highly active in pediatric low-grade gliomas, and that mTOR activity could be blocked using an experimental drug, leading to decreased growth of these tumors. Read more here.

Study mentioned: Hütt-Cabezas M, et al. Activation of mTORC1/mTORC2 signaling in pediatric low-grade glioma and pilocytic astrocytoma reveals mTOR as a therapeutic target. Neuro Oncol. 2013 Nov 6. [Epub ahead of print] PMID: 24203892

HPV can damage genes and chromosomes directly, sequencing study shows

The virus that causes cervical, head and neck, anal and other cancers can damage chromosomes and genes where it inserts its DNA into human DNA, according to a new study led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute. Read more here.

Study mentioned: Akagi K, et al. Genome-wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability. Genome Res. 2013 Nov 7. [Epub ahead of print] PMID: 24201445

Prognostic value of baseline quality-of-life data for survival in different types of cancer

Results of an European Organization for Research and Treatment of Cancer (EORTC) study point out the prognostic value of baseline recorded health-related quality of life for survival in eleven types of cancer: brain, breast, colorectal, oesophageal, head and neck, lung, melanoma, ovarian, pancreatic, prostate, and testicular cancer. For each cancer type, at least one health-related, quality-of-life parameter provided additional prognostic information over and above the clinical and socio-demographic variables. Read more here.

Study mentioned: Quinten C, et al. A global analysis of multitrial data investigating quality of life and symptoms as prognostic factors for survival in different tumor sites. Cancer. 2013 Oct 11. [Epub ahead of print] PMID: 24127333

Friday 8 November 2013

Long term results of EORTC trial of perioperative FOLFOX4 versus surgery alone

Phase III study in patients with resectable liver metastases from colorectal cancer
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Long term results of the randomized phase III EORTC intergroup trial 40983, recently reported in The Lancet Oncology, show that observed 4.1% difference in overall survival at five years for patients with initially resectable liver metastases from colorectal cancer is not significant for perioperative chemotherapy with FOLFOX4 compared with surgery alone. Earlier results of the same study had shown that perioperative chemotherapy with FOLFOX4 increases progression-free survival (PFS), which was the primary endpoint of the study, compared with surgery alone in these patients. Overall survival was a secondary endpoint, and the trial was not initially powered to compare overall survival in the two groups. In this new article, the authors presented overall survival data after long-term follow-up and concluded that no difference in overall survival was found with the addition of perioperative chemotherapy with FOLFOX4. In addition, they wrote that previously observed benefit in PFS means that perioperative chemotherapy with FOLFOX4 should remain the reference treatment in this population of patients. Read more here.

Study mentioned: Nordlinger B, Sorbye H, Glimelius B, et al. Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. The Lancet Oncology 2013, 14(12): 1208-15. doi: 10.1016/S1470-2045(13)70447-9. Epub 2013 Oct 11.

Canadian Breast Cancer Foundation makes $4.77 million research investment in Western Canada

As Canada’s leading community-driven breast cancer charity dedicated to funding relevant, innovative research, and supporting and advocating for the breast cancer community, the Canadian Breast Cancer Foundation – Prairies/NWT Region Thursday announced an investment of more than $4.77 million to support breast cancer research programs.
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A total of 14 research projects – including three at the University of Calgary — will benefit from the grants with funding spanning the next three years. Read more here.

Thursday 7 November 2013

SEMI-NUC project: “Prospective cohort study of residents living near the Semipalatinsk nuclear test site – feasibility assessment”

The International Agency for Research on Cancer (IARC) announces the launch of the web site for the SEMI-NUC project: “Prospective cohort study of residents living near the Semipalatinsk nuclear test site – feasibility assessment”. The two-year project is coordinated by the Section of Environment and Radiation at IARC and supported by the European Commission Euratom FP7 grant No 323310. Read more here.

A pilot study shows next-generation sequencing feasibility in patients with advanced cancers

A pilot study led by the Translational Genomics Research Institute and the Virginia G. Piper Cancer Center at Scottsdale Healthcare shows that, even for patients with advanced and rapidly transforming cancer, next generation sequencing is feasible. While the initial effort was a slower process than anticipated due to a variety of issues, treatments for patients with progressing tumours may be improved. Read more here.

Study mentioned: Weiss GJ, et al. (2013) A Pilot Study Using Next-Generation Sequencing in Advanced Cancers: Feasibility and Challenges. PLoS ONE 8(10): e76438.

A new study evaluates early autologous stem cell transplantation for aggressive non-hodgkin's lymphoma

Performing early stem cell transplantation in patients with aggressive non-Hodgkin's lymphoma does not improve overall survival in high-risk patients, according to a study published on 31 October, 2013 in the New England Journal of Medicine. But early transplantation does appear to be beneficial among a small group of patients who are at the very high risk, the study found. Read more here.

Study mentioned: Stiff PJ, et al. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med. 2013 Oct 31;369(18):1681-90. PMID: 24171516

International osteoporosis foundation working group provides guidance on fracture prevention in cancer-associated bone disease

Bones are often affected in cancer patients, frequently because of bone metastases, or as a result of anti-cancer therapies which can contribute to bone loss and fragility. A new paper published by an International Osteoporosis Foundation Committee of Scientific Advisors Working Group reviews the epidemiology and pathophysiology of cancer-associated bone disease and provides information about fracture prevention in cancer patients. The review summarises the pertinent recommendations of leading societies, providing guidance for clinical decision making and information on evidence-based pathways to prevent skeletal-related events and bone loss. Read more here.

Study mentioned: Rizzoli R, et al. Cancer-associated bone disease. Osteoporos Int. 2013 Oct 22. [Epub ahead of print] PMID: 24146095