Jennifer Palisoc

Clinical trial delivers chemotherapy to pediatric brain tumours using MRI-guided focused ultrasound

Christopher.Sorensen — Mon, 23 Jan 2023 19:42:20 +0000

Clinical trial delivers chemotherapy to pediatric brain tumours using MRI-guided focused ultrasound

Christopher.Sorensen Mon, 01/23/2023 - 14:42

Cutline

A brain scan shows an MRI-guided focused ultrasound opening the blood-brain barrier for delivery of chemotherapy to a common brain tumour in children (photo courtesy of Sunnybrook)

Jennifer Palisoc

Jessamine Luck

Topic

Breaking Research

Sunnybrook Health Sciences

Temerty Faculty of Medicine

Hospital for Sick Children

Research & Innovation

A team of Toronto researchers and physicians are the first in the world to use MRI-guided focused ultrasound to open the blood-brain barrier and deliver chemotherapy to treat Diffuse Intrinsic Pontine Glioma (DIPG), an aggressive and terminal pediatric brain tumour.

The first pediatric patient recently successfully underwent the procedure as part of a safety and feasibility clinical trial in children with this tumour.

A challenge for treatment of DIPG is the blood-brain barrier, a protective network of cells, which can prevent therapeutics from reaching areas in the brain. In this Phase 1 clinical trial, low-intensity focused ultrasound technology is used to temporarily open the blood-brain barrier with the power of soundwaves, allowing drug treatment to cross and treat the brain tumour.

“DIPG is a devastating pediatric brain tumour which is inoperable due to its location in the brainstem,” says Nir Lipsman, a neurosurgeon and director of the Harquail Centre for Neuromodulation at Sunnybrook Health Sciences Centre who is a co-principal investigator of the study. “Focused ultrasound is an innovative and non-invasive approach to more effectively delivering chemotherapy directly to the tumour. Our hope is that this continued research will bring us closer to enhancing treatments to help change the course of the disease.”

Lipsman is also an associate professor of surgery at the 91�Թ�’s Temerty Faculty of Medicine.

The goal of the clinical trial is to safely and temporarily open the blood-brain barrier, a layer of cells, to deliver chemotherapy to the tumour with MRI-guided focused ultrasound (photo courtesy of Sunnybrook Health Sciences Centre)

“Current treatment for DIPG is limited to radiation, which can slow progression of the tumour for a period of time, but does not have longer-term effects,” says James Rutka, study co-principal investigator and director of the Arthur and Sonia Labatt Brain Tumour Research Centre at The Hospital for Sick Chlidren (SickKids).

“Focused ultrasound technology is a promising drug-delivery strategy that is helping us penetrate the blood-brain barrier in a novel way,” adds Rutka, who is also a professor of surgery at Temerty Medicine. “Conducting this trial will help us build new and innovative treatment pathways for children with DIPG.”

DIPG tumours are the most common form of brain tumour in children under the age of 15 and make up nearly 10 to 15 per cent of all childhood brain tumours. It affects the region of the brainstem known as the pons, which regulates the body’s involuntary activities such as breathing, heart rate and important functions such as swallowing. DIPG is considered a terminal cancer.

Clinical and research teams from Sunnybrook and SickKids are collaborating on the clinical trial, which investigates the safety and feasibility of breaching the blood-brain barrier using MRI-guided focused ultrasound in combination with the delivery of chemotherapy in pediatric patients with DIPG.

Nir Lipsman, left, and James Rutka, right (photo courtesy of Sunnybrook)

The study includes 10 patients between five and 18 years old who have been diagnosed with DIPG. Study participants receive general anesthesia ahead of focused ultrasound treatment at Sunnybrook, which will involve three cycles of chemotherapy about four to six weeks apart. A specialized helmet is used to deliver ultrasound energy to brain targets without requiring scalpels or incisions. SickKids physicians and nurses will assist with the treatment procedure at Sunnybrook, and the children will receive post-operative care at SickKids.

Low-intensity ultrasound interacts with microscopic bubbles that vibrate causing a temporary opening in the blood-brain barrier, enabling therapies to pass and reach a targeted area. The blood brain barrier closes within hours of the procedure.

In 2015, Sunnybrook researchers were the first in the world to investigate low-intensity focused ultrasound in the opening of the blood-brain barrier and delivery of chemotherapy in adult brain cancer, and recently demonstrated in a trial that chemotherapy can be delivered across the blood brain barrier in brain metastases.

A team of researchers from Sunnybrook and SickKids monitor progress during treatment (photo courtesy of Sunnybrook)

Sunnybrook has also continued this leading-edge focused ultrasound research in other debilitating brain disease, including Parkinson’s disease, Alzheimer’s disease, Amyotrophic Lateral Sclerosis, major depression and other disorders.

This study was funded and supported by the Harquail family through the Harquail Centre for Neuromodulation; the Focused Ultrasound Foundation; and INSIGHTEC as well as by its lead donor at SickKids; Jordana’s Rainbows Foundation and the Fiorini family' Meagan’s Hug; Nelina’s Hope; and the Wiley family, who supported pre-clinical trial work.

This story originally appeared at the Hospital for Sick Children and Sunnybrook Health Sciences Centre.

Read a Q&A with the researchers in Maclean’s magazine

91�Թ�, Sunnybrook researchers deliver ultrasound-guided cancer therapy to the brain

Christopher.Sorensen — Wed, 13 Oct 2021 14:08:38 +0000

91�Թ�, Sunnybrook researchers deliver ultrasound-guided cancer therapy to the brain

Christopher.Sorensen Wed, 10/13/2021 - 10:08

Cutline

A brain scan confirms that an antibody therapy designed to treat breast cancer reached targeted tumours that had spread to the brain (photo courtesy of the Sunnybrook Health Sciences Centre)

Jennifer Palisoc

Topic

Breaking Research

Sunnybrook Health Sciences

Temerty Faculty of Medicine

Cancer

Leslie Dan Faculty of Pharmacy

Research & Innovation

Researchers at Sunnybrook Health Sciences Centre and the 91�Թ� have demonstrated the safe delivery of an antibody therapy across the blood-brain barrier using MRI-guided focused ultrasound.

The research team captured images of Trastuzumab, an antibody therapy drug, precisely targeting tumours that spread to the brain from breast cancer across the blood-brain barrier. The blood-brain barrier is a thin layer of cells that protects the brain from toxins and other viruses and bacteria – but also blocks helpful therapies from reaching the brain.

The study is published in Science Translational Medicine.

Nir Lipsman

“This is the first visual confirmation that focused ultrasound can improve the delivery of targeted antibody therapy across the blood-brain barrier,” says Nir Lipsman, the study’s principal investigator, director of the Harquail Centre for Neuromodulation at Sunnybrook and an associate professor in the department of surgery in 91�Թ�’s Temerty Faculty of Medicine.

“These are preliminary, but very promising, results that with continued research have implications well beyond brain cancer and to other neurological conditions.”

The study’s researchers used an innovative approach to confirm the drug’s delivery on brain scans. Trastuzumab was radio-labelled, meaning the antibody therapy was “tagged” chemically to emit a signal that could be easily visualized using single photon emission computerized tomography (SPECT) imaging, a form of imaging commonly used in nuclear medicine. Scans performed before the procedure as well as after showed significantly increased uptake of antibody therapy after focused ultrasound.

Raymond Reilly

The radiopharmaceutical drug was developed by Professor Raymond Reilly and his team at 91�Թ�’s Leslie Dan Faculty of Pharmacy. “We applied our expertise in radio-labelling of Trastuzumab to enable the team at Sunnybrook for the first time to track the delivery of the drug across the blood-brain-barrier into the brain after applying MRI-guided focused ultrasound,” says Reilly, who is also the director of the Centre for Pharmaceutical Oncology at 91�Թ�. “Radiopharmaceuticals are very powerful tools to visualize the delivery of anti-cancer drugs to tumours.

“Radiopharmaceuticals are also used to detect cancer and may be extended to treatment of cancer – they are a very versatile tool.”

MRI-guided focused ultrasound technology uses ultrasound waves to non-invasively and temporarily open the blood-brain barrier enabling therapeutics to reach specified areas of the brain. The study results set the stage for the possibility of delivering a host of both established and novel therapies for numerous brain conditions that would otherwise be unable to access the brain.

A helmet-like focused ultrasound device, developed by InSightec, was used in conjunction with MRI guidance in four patients in this phase one trial to direct ultrasound waves precisely to areas of the brain where tumours were clearly visualized. While in the MRI machine, participants received the radio-labelled Trastuzumab, a compound that is 100 times larger than the typical compound that can enter the brain across the blood-brain barrier. Focused ultrasound was used to temporarily open the blood-brain barrier to allow the passage of the antibody therapy, into the tumor tissue.

“This is a breakthrough moment in the field of focused ultrasound. It is the result of incredible collaboration among various teams over the past two decades, including oncology, surgery, pharmacy, nuclear medicine, neuroradiology, medical physics and more,” says Kullervo Hynynen, vice-president, research and innovation, Sunnybrook Research Institute and a professor of medical biophysics at 91�Թ�’s Temerty Faculty of Medicine. “It is a great story of preclinical to clinical research and the dedication of investigators to find innovative ways to personalize treatment for patients in the future.”

Metastatic breast cancer, also known as stage-four breast cancer, starts in the breast and spreads to other areas of the body, which can include the bone, liver or other organs, and the brain. It’s estimated that brain metastases in patients with Her2-positive breast cancer are increasing in prevalence by approximately 30 per cent and are associated with greater morbidity and mortality despite therapeutic advances.

At present, breast cancer brain metastases are treated with a combination of open neurosurgery, radiation and chemotherapy. However, depending on the location and number of brain metastases, options for surgery and radiation may be limited and it can be difficult for therapy to penetrate tumours in the brain.

“The early data in this study suggests delivery of antibody therapy directly to tumours using focused ultrasound may impact treatment efficacy, with tumours slightly decreasing in size, with varying results for patients between seven to 31 per cent during the study – on average to 21 per cent,” says Rossanna Pezo, medical oncologist in the Odette Cancer Centre at Sunnybrook and an assistant professor in the department of medicine at 91�Թ�’s Temerty Faculty of Medicine. “The reduction in tumour size is promising but should be interpreted with caution as further research on a larger scale is needed.”

Study shows increase in suicide among young women after Netflix series 13 Reasons Why

Christopher.Sorensen — Mon, 03 Jun 2019 20:28:33 +0000

Study shows increase in suicide among young women after Netflix series 13 Reasons Why

Christopher.Sorensen Mon, 06/03/2019 - 16:28

Cutline

“The tragedy is that this outcome was predictable,” says study co-author Mark Sinyor, an assistant professor of psychiatry at the 91�Թ� and a psychiatrist at Sunnybrook Health Sciences Centre (photo by Doug Nicholson)

Topic

Research & Innovation

Sunnybrook Hospital

A study by an international research group has found that suicides spiked in youth – particularly young women – after the release of the Netflix series 13 Reasons Why, which portrays the suicide of a teenage girl.

The time-series analysis found a 13 per cent increase in suicides among 10- to 19-year-olds in the United States three months after the show’s release, or 94 more suicides than expected.

The researchers hypothesized that the increase would be most pronounced in young women since the main character who dies by suicide in the series is a teen girl in high school. The study found a 22 per cent increase in suicides among young women in the same age group during that time.

“If youth, some of whom are at risk, are exposed to this kind of content which we know to be misleading and dangerous, they may identify with what the character is going through and mistakenly think that suicide is the only option,” says study co-author Mark Sinyor, an assistant professor of psychiatry at the 91�Թ� and a psychiatrist at Sunnybrook Health Sciences Centre.

“But there is no reason that has to happen. The series 13 Reasons Why failed to show that suicide almost always arises from a treatable mental illness,” says Sinyor. “People need to know that there is help and that suicide can be prevented.”

The journal JAMA Psychiatry recently p ublished the findings.

Researchers from Austria, Canada, the U.S. and Australia analyzed suicide data and social media analytics from the show’s launch in April to June 2017, when interest in the series was strongest.

“While caution must be taken in interpreting any association, the direction and magnitude of effect observed here are all consistent with what would be expected if 13 Reasons Why was producing a contagion effect,” says Thomas Niederkrotenthaler, the study’s lead author and suicide research group lead at the Medical University of Vienna.

Suicide contagion can occur when harmful information about suicide is prominent in media and entertainment domains. But experts say that more scientifically accurate portrayals emphasizing hope and resilience can lead to contagion of positive coping strategies and can help save lives.

“It is vital that the entertainment industry takes this issue seriously. Research has shown that when the media shares stories of people finding ways to cope with suicidal crises, and provides information about how to get help, people will also copy that behaviour,” says Sinyor.

With mounting evidence pointing to a rising trend in youth suicides following 13 Reasons Why, researchers say there is a need for improved collaboration between the entertainment industry and suicide prevention experts regarding the portrayals of suicide.

“These findings raise concern and reinforce that strong collaborations could result in on-screen portrayals that potentially act as a force for good in suicide prevention,” says Niederkrotenthaler.

“The tragedy is that this outcome was predictable,” adds Sinyor. “Hopefully this will be a wake-up call to the entertainment industry that we desperately need them to help disseminate accurate and healthy messages about mental health and to stop sending potentially harmful ones. No one wants to see more children die and there is absolutely no reason they need to. We already have the information we need to make sure that messages we send our youth are safe.”

Read a Q&A with 91�Թ�’s Mark Sinyor and Ayal Schaffer about reporting on suicide and the importance of focusing on resilience

Women less likely to be diagnosed with minor stroke than men: 91�Թ� study

Christopher.Sorensen — Tue, 28 May 2019 18:05:32 +0000

Women less likely to be diagnosed with minor stroke than men: 91�Թ� study

Christopher.Sorensen Tue, 05/28/2019 - 14:05

Cutline

The study found that women were 10 per cent more likely to be given a non-stroke diagnosis – for example migraine or vertigo – even though men and women were equally likely to report atypical stroke symptoms (photo by Mayte Torres via Getty Images)

Topic

Research & Innovation

Stroke

Sunnybrook Hospital

Women experiencing a minor stroke or transient ischemic attack (TIA) are less likely to be diagnosed with a stroke compared to men – even though they describe similar symptoms in emergency departments.

That’s according to a 91�Թ�-led study published in JAMA Neurology that was presented at the European Stroke Organisation Conference in Milan on May 22.

The study found men and women equally described atypical stroke symptoms such as dizziness, tingling or confusion, but that women were more likely than men to be diagnosed with another ailment.

“In our study, men were more likely to be diagnosed with TIA or minor stroke, and women were 10 per cent more likely to be given a non-stroke diagnosis – for example migraine or vertigo – even though men and women were equally likely to report atypical stroke symptoms,” says study lead author Dr. Amy Yu, a stroke neurologist at Sunnybrook Health Sciences Centre and assistant professor at the 91�Թ�’s department of medicine in the Faculty of Medicine.

A TIA occurs when there is temporary interruption of blood flow to the brain, and is often a warning sign of another stroke. TIAs can also be associated with permanent disability. Typical symptoms of stroke, by contrast, are sudden weakness, face drooping or speech difficulties.

“Our study also found the chance of having another stroke or heart attack within 90 days of the diagnosis was the same for women and men,” adds Dr. Shelagh Coutts, a stroke neurologist with Alberta Health Services at Foothills Medical Centre and an associate professor at the University of Calgary’s Cumming School of Medicine.

Researchers say that, while further study is needed, it’s possible patient reporting of symptoms, interpretation of symptoms by clinicians, or a combination of both, could explain the discrepancy in diagnosis among men and women.

“Our findings call attention to potential missed opportunities for prevention of stroke and other adverse vascular events such as heart attack or death in women,” says Coutts.

Previous studies on this topic have focused on patients diagnosed with stroke. Researchers in the current study included 1,648 patients with suspected TIA who were referred to a neurologist after receiving emergency care from 2013 to 2017, regardless of their final diagnosis.

Researchers note it is an important opportunity for the public and clinicians to be aware of atypical symptoms of TIA.

“What’s important to recognize in stroke is that the brain has so many different functions and when a stroke is happening, people can feel different things beyond the typical stroke symptoms,” says Yu.

“Accurately diagnosing TIA and stroke would change a patient’s treatment plan and could help prevent another stroke from happening.”