MR images showing a patient with recurrent glioblastoma responding to anti-angiogenic therapy by reduction on abnormal tumor vessel calibers and a change in the direction of the vessel vortex curve estimated from a combined gradient-echo (GE) and spin-echo (SE) MR signal readout. The change from a predominantly counter-clockwise vessel vortex direction at baseline (days -5 and -1) to a predominantly clockwise vessel vortex direction during anti-angiogenic therapy (days 1, 28, 56 and 112) indicates a dramatic transformation in vascular morphology during anti-angiogenic therapy and resulting in increased overall survival. Credit: Kyrre E. Emblem
A new way of analyzing data acquired in MR imaging appears to be able to identify whether or not tumors are responding to anti-angiogenesis therapy, information that can help physicians determine the most appropriate treatments and discontinue ones that are ineffective. In their report receiving online publication in Nature Medicine, investigators from the Martinos Center for Biomedical Imaging at Massachusetts General Hospital (MGH), describe how their technique, called vessel architectural imaging (VAI), was able to identify changes in brain tumor blood vessels within days of the initiation of anti-angiogenesis therapy.
“Until now the only ways of obtaining similar data on the blood vessels in patients’ tumors were either taking a biopsy, which is a surgical procedure that can harm the patients and often cannot be repeated, or PET scanning, which provides limited information and exposes patients to a dose of radiation,” says Kyrre Emblem, PhD, of the Martinos Center, lead and corresponding author of the report. “VAI can acquire all of this information in a single MR exam that takes less than two minutes and can be safely repeated many times.”
Previous studies in animals and in human patients have shown that the ability of anti-angiogenesis drugs to improve survival in cancer therapy stems from their ability to “normalize” the abnormal, leaky blood vessels that usually develop in a tumor, improving the perfusion of blood throughout a tumor and the effectiveness of chemotherapy and radiation. In the deadly brain tumor glioblastoma, MGH investigators found that anti-angiogenesis treatment alone significantly extends the survival of some patients by reducing edema, the swelling of brain tissue. In the current report, the MGH team uses VAI to investigate how these drugs produce their effects and which patients benefit.
Advanced MR techniques developed in recent years can determine factors like the size, radius and capacity of blood vessels. VAI combines information from two types of advanced MR images and analyzes them in a way that distinguishes among small arteries, veins and capillaries; determines the radius of these vessels and shows how much oxygen is being delivered to tissues. The MGH team used VAI to analyze MR data acquired in a phase 2 clinical trial – led by Tracy Batchelor, MD, director of Pappas Center for Neuro-Oncology at MGH and a co-author of the current paper – of the anti-angiogenesis drug cediranib in patients with recurrent glioblastoma. The images had been taken before treatment started and then 1, 28, 56, and 112 days after it was initiated.
In some patients, VAI identified changes reflecting vascular normalization within the tumors – particularly changes in the shape of blood vessels – after 28 days of cediranib therapy and sometimes as early as the next day. Of the 30 patients whose data was analyzed, VAI indicated that 10 were true responders to cediranib, whereas 12 who had a worsening of disease were characterized as non-responders. Data from the remaining 8 patients suggested stabilization of their tumors. Responding patients ended up surviving six months longer than non-responders, a significant difference for patients with an expected survival of less than two years, Emblem notes. He adds that quickly identifying those whose tumors don’t respond would allow discontinuation of the ineffective therapy and exploration of other options.
Gregory Sorensen, MD, senior author of the Nature Medicine report, explains, “One of the biggest problems in cancer today is that we do not know who will benefit from a particular drug. Since only about half the patients who receive a typical anti-cancer drug benefit and the others just suffer side effects, knowing whether or not a patient’s tumor is responding to a drug can bring us one step closer to truly personalized medicine – tailoring therapies to the patients who will benefit and not wasting time and resources on treatments that will be ineffective.” Formerly with the Martinos Center, Sorensen is now with Siemens Healthcare.
Study co-author Rakesh Jain, PhD, director of the Steele Laboratory in the MGH Department of Radiation Oncology, adds, “This is the most compelling evidence yet of vascular normalization with anti-angiogenic therapy in cancer patients and how this concept can be used to select patients likely to benefit from these therapies.”
Lead author Emblem notes that VAI may help further improve understanding of how abnormal tumor blood vessels change during anti-angiogenesis treatment and could be useful in the treatment of other types of cancer and in vascular conditions like stroke. He and his colleagues are also exploring whether VAI can identify which glioblastoma patients are likely to respond to anti-angiogenesis drugs even before therapy is initiated, potentially eliminating treatment destined to be ineffective. A postdoctoral research fellow at the Martinos Center at the time of the study, Emblem is now a principal investigator at Oslo University Hospital in Norway and maintains an affiliation with the Martinos Center.
I recently found out that one of my dearest friends has a brain tumor. He’s getting it removed this week, but he’s only 29 and the whole thing is just wildly depressing and honestly completely fucking shocking. He’s on Medicaid, and he won’t be able to work for at least a month after his surgery — plus we have no idea if they’ll be able to remove the whole tumor and if he’ll need chemo and radiation when all is said and done. The harsh reality is that this could be the first of several surgeries.
Hugh, my buddy, is one of the nicest people I’ve ever met. He was there for me when I had COVID, literally the only person who visited me when I was sick. He spent most of 2020 unemployed and volunteering to delivery groceries to high risk folks in our neighborhood while also organizing for Black Lives Matter.
His activism, open-heartedness, and die-hard baseball fanaticism make him an easy guy to love. He’s also a charming, sane member of the kink community and always ready with a story or advice. His friendship means the world to me.
All this to say, there’s a GoFundMe for Hugh and I know it’s a lot to ask, but every little bit counts and if you might be willing to donate what you can to a stranger I would be forever grateful. And no matter what, I hope you might share this post for me and for Hugh. I hate that America is the kind of place where this is necessary, but such is the world we live in.
These are not all the symptoms of brain cancer, and brain cancer is NOT the only cause of these symptoms. If you suddenly or frequently experience any of these, go to your doctor so they can determine the cause.
[ID: An illustration of the side view of the human brain, with each lobe colored differently, with the most common symptoms arranged to follow the shape of the brain/lobes. The lobe-specific symptoms of brain cancer are in list formats outside the brain and correlate in color to the lobes. Frontal lobe: Personality changes, Increased aggression/irritation, Apathy, Weakness on one side of the body, Loss of smell, Difficulty walking, and Vision / Speech problems. Parietal lobe: Difficulty speaking/understanding, Problems reading/writing, and Loss of feeling in part of the body. Occipital lobe: Vision problems. Meninges: Headache, Nausea/vomiting, Sight problems, and Neck pain. Pituitary Gland: Lack of energy, Weight gain, Mood swings, High blood pressure, Diabetes, Enlarged hands/feet, Irregular/infrequent periods, and Infertility/impotence. Temporal lobe: Forgetting words, Short-term memory loss, and Seizures (often associated with strange smells/feelings). Brain Stem: Issues with coordination, Eyelid/mouth droops to one side, Difficulty swallowing, Difficulty speaking, and Double vision. Cerebellum: Issues with coordination, Uncontrolled eye movement, Nausea/vomiting, Neck stiffness, and Dizziness. Spinal Cord: Pain, Numbness, Weakness in legs/arms, Loss of bladder/bowel control, and Difficulty walking. End description.]
