They say ‘a picture is worth a thousand words.’ In medical imaging—where images are used by doctors to guide therapies—two pictures may be even more valuable than one.
That is what a team of researchers at the Princess Margaret Cancer Centre found when they combined two types of medical imaging techniques, positron emission tomography (PET) and computed tomography (CT), to diagnose lymphoma patients.
While CT scans provide location and structural information about an individual’s tumour, PET is used to visualize cellular metabolism—a useful strategy for detecting fast growing cancerous cells. This complete snapshot of an individual’s tumor can help determine its location and severity (known as ‘staging’) prior to therapy, allowing clinicians to plan effective treatment.
“Despite recent guidelines that recommend PET/CT versus CT alone for more accurate staging of patients with lymphoma, the value of using PET imaging in addition to CT on clinical outcomes is not fully clear,” says Dr. Ur Metser, Division Head of Molecular Imaging at Princess Margaret Cancer Centre and Core Lead at the Techna Institute.
To address this knowledge gap, the research team compared the effect that PET/CT staging versus CT staging alone had on the management and outcomes of 850 individuals with lymphoma.
The added information provided by combined imaging with PET/CT changed the disease stage from “early” to “advanced” in about one in five of these patients. This changed treatment plans in around four out of ten participants. Importantly, for patients with aggressive non-Hodgkin’s lymphoma treated according to PET/CT data, there was improved survival at one-year compared to those treated according to CT alone.
“In this study, we were able to demonstrate the importance of accurate staging of lymphomas, which allows clinicians to effectively manage and plan treatment,” says Dr. Metser. “Adding PET imaging to a patient’s medical examination for certain types of lymphoma can significantly impact their survival.”
This work was supported by Ontario Ministry of Health and Long-Term Care (MOHLTC), Cancer Care Ontario and The Princess Margaret Cancer Foundation.
Metser U, Prica A, Hodgson D, Mozuraitis M, Eberg M, Mak V, Green B, Singnurkar A, Dudebout J, MacCrostie P, Tau N, Mittmann N, Langer DL. Effect of PET/CT on the management and outcomes of participants with Hodgkin and aggressive non-Hodgkin lymphoma. Radiology. 2018 Dec 4. doi: 10.1148/radiol.2018181519.
Dr. Aaron Schimmer MD, PhD, FRCPC has been appointed as the new Research Director of the Princess Margaret Cancer Centre, effective February 15, 2019.
Dr. Schimmer has been an active clinician and a researcher at PM since 2003, where he has established a vibrant translational research program in developing innovative therapeutic strategies to target leukemia and leukemia stem cells.
He is a highly productive and recognized authority in the cancer research field, with over 217 peer-reviewed papers published over the course of his career, with many in high impact journals like Cancer Cell and Blood. His work in novel therapeutics has resulted in over 15 patents and patent applications and, to date, he has advanced three candidate therapeutic drugs from his lab into Phase I clinical trials.
He is also the recipient of numerous prestigious research awards, including the Till and McCulloch Award and the Bernard and Francine Dorval Prize.
Dr. Schimmer has a long list of contributions to research, clinical practice and education at UHN and the University of Toronto that is a testament to his commitment to science and research here in Toronto—an essential element for success in this new role. He has demonstrated a commitment to supporting his colleagues and to advancing the impact of Princess Margaret on the global stage.
Congratulations Dr. Schimmer!
Much like how location can directly affect the price of a home, targeting specific areas of the brain can have an effect on the success of certain brain treatments. However, delivering treatment to the exact location in the brain that will provide the most benefit remains a daunting challenge.
To help address this challenge, researchers at Krembil Research Institute explored an emerging technique, known as magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy, for the treatment of essential tremor—a debilitating brain disorder that causes uncontrollable shaking. This study was done in collaboration with Sunnybrook Health Sciences Centre.
The approach uses high-resolution MR imaging to precisely target a tiny area of the brain called the thalamus. This brain region is responsible for relaying important motor and sensory signals in the brain and is a key target for essential tremor therapies.
By examining patients who underwent MRgFUS thalamotomy, the study found that clinical outcomes were largely dependent on the specific regions that were targeted within the thalamus. Just as in the real estate market, location seems to play a critical role in the clinical outcomes of these patients.
The researchers further mapped out areas that were associated with the best treatment responses, as well as those linked with an increased risk of detrimental side effects. Using standard assessment methods, the research team found that use of MRgFUS led to a ~42% improvement in tremor scores three months after treatment. The study also suggested that when smaller areas of the brain were targeted, side effects were less severe.
“These findings are a significant step toward improving the effectiveness of MRgFUS thalamotomy and will enable us to refine areas to target therapy so that we can improve outcomes and reduce adverse effects for patients,” says Dr. Andres M. Lozano, a neurosurgeon at Toronto Western Hospital and Krembil Senior Scientist.
This work was supported by Insightec and the Toronto General & Western Hospital Foundation. Dr. Lozano holds a Tier 1 Canada Research Chair in Neuroscience.
Boutet A, Ranjan M, Zhong J, Germann J, Xu D, Schwartz ML, Lipsman N, Hynynen K, Devenyi GA, Chakravarty M, Hlasny E, Llinas M, Lozano CS, Elias GJB, Chan J, Coblentz A, Fasano A, Kucharczyk W, Hodaie M, Lozano AM. Focused ultrasound thalamotomy location determines clinical benefits in patients with essential tremor. Brain. 2018 Dec 1. doi: 10.1093/brain/awy278.
Finland is known for its snowy landscapes and herds of reindeer.
In 2014, Finland became famous for a very different reason: researchers discovered Finnish people carrying a new type of mutation—known as A53E—in the SNCA gene that causes Parkinson disease (PD).
PD is a neurodegenerative disease characterized by progressive problems with movement. Many people with PD will also experience impaired mental function. Some hereditary forms of the disease are caused by mutations in the SNCA gene and may develop at a younger age than non-hereditary forms. To date, at least 6 different SNCA mutations have been detected in PD patients.
Until recently, the A53E mutation had only been found in Finnish families with PD.
In November 2018, Dr. Lorraine Kalia, a neurologist and Scientist at the Krembil Research Institute, reported the discovery of a Canadian family with PD caused by the A53E mutation. This work was done in collaboration with colleagues at the Krembil, the Morton and Gloria Shulman Movement Disorders Clinic and Edmond J. Safra Program in Parkinson’s Disease at Toronto Western Hospital, and the Tanz Centre for Research in Neurodegenerative Diseases at the University of Toronto.
Using genetic tests and the family’s medical history, Dr. Kalia and her colleagues found that the A53E mutation is likely to have occurred spontaneously and was not inherited from a Finnish ancestor. The tests also suggest that the pattern of methyl molecules ‘decorating’ the patients’ DNA might contribute to the earlier appearance of symptoms in PD patients with SNCA mutations.
Given that the SNCA gene provides the instructions for making the protein α-synuclein, Dr. Kalia and her colleagues also examined the effect of the A53E mutation on the protein’s behaviour in test tubes and in cells.
They showed that the mutated proteins had an increased tendency to form ‘clumps’ and that attaching a phosphoryl molecule onto the proteins caused them to assemble into ‘fibres’. Similar clumps and fibres of α-synuclein are typically found in the brains of PD patients and are believed to be toxic to brain cells and thus are key contributors to neurodegeneration.
Of the findings, Dr. Kalia says, “They show that the A53E mutation should not be ruled out as a cause of Parkinsonism outside of Finland. They also provide new insights into the mechanisms underpinning Parkinson disease, as well as other neurological diseases involving α-synuclein.”
This work was supported by the Canadian Institutes of Health Research, the Canadian Consortium on Neurodegeneration in Aging, and the Toronto General & Western Hospital Foundation (TGWHF).
Picillo M, Lizarraga KJ, Friesen EL, Chau H, Zhang M, Sato C, Rooke G, Munhoz RP, Rogaeva E, Fraser PE, Kalia SK, Kalia LV. Parkinsonism due to A53E α-synuclein gene mutation: Clinical, genetic, epigenetic, and biochemical features. Mov Disord. 2018 Nov 13. doi: 10.1002/mds.27506.
A team of researchers and clinicians specializing in head-and-neck cancer has identified a way to manipulate metabolism to potentially prevent skin fibrosis—a common side effect of radiotherapy affecting quality of life of cancer survivors.
The findings, from the laboratory of Princess Margaret Cancer Centre Senior Scientist Dr. Fei-Fei Liu, were published online today in Nature Metabolism.
First author Dr. Xiao Zhao, a resident in head-and- neck surgery who completed his PhD studies with Dr. Liu, says the research team wanted to find a way to reduce radiation-induced fibrosis, a condition where normal tissue progressively thickens causing pain and dysfunction. The underlying problem is the excess buildup of the extracellular matrix, a supporting structure for all tissues. There is currently no effective treatment to reduce this accumulation.
The team used human tissues with radiation-induced fibrosis and pre-clinical experiments to identify metabolic processes as key triggers and promoters of fibrosis. Metabolic processes are responsible for breaking down fats, proteins and sugars to provide cellular energy. Dr. Zhao explains, “We were surprised to see that metabolic abnormalities were predominant and consistently found in patients with skin fibrosis, even years after their original radiotherapy. Our question was: ‘Can we manipulate metabolism to reduce fibrosis?’”
The team identified two metabolic pathways that were consistently altered in skin with fibrosis: one pathway involved in the breakdown of fats was less active relative to healthy skin; and a second pathway involved in the breakdown of sugar was more active than in healthy skin.
Through uncovering this metabolic model of extracellular matrix regulation, the team also identified several metabolic drug compounds and potential cell therapy techniques that reduced fibrosis in pre-clinical models.
“We’re highlighting fibrosis from this new perspective, thereby opening the door to metabolic regulation as a way to treat this side effect of radiation,” says Dr. Zhao.
Source: UHN.ca
Xiao Zhao, Pamela Psarianos, Laleh Soltan Ghoraie, Kenneth Yip, David Goldstein, Ralph Gilbert, Ian Witterick, Hilary Pang, Ali Hussain, Ju Hee Lee, Justin Williams, Scott V. Bratman, Laurie Ailles, Benjamin Haibe-Kains and Fei-Fei Liu. Metabolic regulation of dermal fibroblasts contributes to skin extracellular matrix homeostasis and fibrosis. Nature Metabolism, 2019; 1 (1): 147 DOI: 10.1038/s42255-018-0008-5
This work was supported by Canadian Institutes of Health Research, the Canadian Cancer Society Research Institute, Physicians Services Incorporated Foundation, the Harry Barberian Research Grant, the Jessie & Julie Rasch Foundation, the Strategic Training in Transdisciplinary Radiation Science for the 21st Century (STARS21), the Campbell Family Cancer Research Institute, the Ontario Ministry of Health and Long-Term Care, and The Princess Margaret Cancer Foundation.
Blood tests to measure 'bad’ cholesterol are common and used to identify the risk of a heart attack. Now researchers are exploring whether other types of fat molecules (ie, lipids) found in the blood can provide new insight into heart health.
One of the researchers advancing this field is Dr. Krista Lanctôt, an Affiliate Scientist at Toronto Rehabilitation Institute and Senior Scientist at Sunnybrook Health Sciences Centre.
Dr. Lanctôt led a recent study that showed that blood levels of lipids known as sphingolipids could serve as a readout of improvements in fitness in patients undergoing cardiac rehabilitation.
“Cardiac rehabilitation is an important way to improve the health of patients with coronary artery disease. However, patients’ response to these programs can be highly variable, which is why we explored whether we could identify a new, more objective way to gauge cardiac fitness in this these patients,” explains Dr. Lanctôt. “We focused on sphingolipids because levels of these lipids were recently shown to be elevated in elderly individuals with poor cardiopulmonary fitness.”
The study enrolled 100 patients with a history of coronary artery disease who were participating in a six-month cardiac rehabilitation program. In these patients, the researchers measured blood levels of 45 different sphingolipids, as well as cardiopulmonary fitness at the beginning of the program and then again at three and six months.
Cardiopulmonary fitness, which is a readout of how well the body uses oxygen during vigorous and sustained workout, was measured using a ‘stress test’, where participants wear a mask to measure oxygen levels while rigorously exercising.
“Our results revealed that blood levels of five key sphingolipids decrease as cardiopulmonary fitness improves during cardiac rehabilitation,” said Dr. Lanctôt. “The findings, while emphasizing the importance of lifestyle changes to improve heart health, also provide detailed data that will inform future studies on the role that sphingolipids play in cardiovascular health.”
Supported by the Canadian Institutes of Health Research, the Alzheimer's Society of Canada, the National Institutes of Health (including the National Institute on Aging), and the Toronto Rehab Foundation. AC Andreazza holds a Tier 2 Canada Research Chair in Molecular Pharmacology of Mood Disorders.
Saleem M, Herrmann N, Dinoff A, Marzolini S, Mielke MM, Andreazza A, Oh [no-lexicon]PI[/no-lexicon], Vattem Venkata SL, Haughey NJ, Lanctôt KL. Association between sphingolipids and cardiopulmonary fitness in coronary artery disease patients undertaking cardiac rehabilitation. J Gerontol A Biol Sci Med Sci. 2018 Dec 8. doi:10.1093/gerona/gly273.
