- Developing Therapies for Brain Tumors: The Impact of the Johns Hopkins Hunterian Neurosurgical Research Laboratory
- Combination drug therapy for childhood brain tumors shows promise in laboratory models: Researchers say findings support use in clinical trials
- My Husband Died From Brain Cancer. Johns Hopkins Medicine Should Be Ashamed, Not Me
- Brain Tumors: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
- Brain Tumor Experts
- About Brain Cancer
- Diagnostic Tests
- Cancer Symptoms
- Current Treatments
- New Treatment Approaches
- Cytomegalovirus (CMV) Research
- Brain Cancer Survivorship
- Could Canine Patients Help Find A Cure For One Of The Deadliest Cancers?
- Brain Tumor Experts | Johns Hopkins Comprehensive Brain Tumor Center
- Nurses and Physician Assistants
Developing Therapies for Brain Tumors: The Impact of the Johns Hopkins Hunterian Neurosurgical Research Laboratory
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Combination drug therapy for childhood brain tumors shows promise in laboratory models: Researchers say findings support use in clinical trials
In experiments with human cells and mice, researchers at the Johns Hopkins Kimmel Cancer Center report evidence that combining the experimental cancer medication TAK228 (also called sapanisertib) with an existing anti-cancer drug called trametinib may be more effective than either drug alone in decreasing the growth of pediatric low-grade gliomas. These cancers are the most common childhood brain cancer, accounting for up to one-third of all cases. Low grade pediatric gliomas arise in brain cells (glia) that support and nourish neurons, and current standard chemotherapies with decades-old drugs, while generally effective in lengthening life, often carry side effects or are not tolerated. Approximately 50% of children treated with traditional therapy have their tumors regrow, underscoring the need for better, targeted treatments.
The combination therapy, when tested in tumor cell lines derived from children's gliomas, stopped the tumor cells from growing. In mice, these drugs reduced tumor volume and allowed mice to live longer, the researchers say.
Mice treated with the combination of drugs also had greatly decreased blood supply to their tumors, suggesting that treatment can starve tumors of the blood they need to grow.
The research, described online in the journal Neuro-Oncology in December 2019, suggests that a clinical trial combining these agents in children would be beneficial, the investigators add.
“We thought one plus one might well equal three in the case of these drugs, and that's what we found,” says senior study author and pediatric oncologist Eric Raabe, M.D., Ph.D., of Johns Hopkins Kimmel Cancer Center, and associate professor of oncology at the Johns Hopkins University School of Medicine.
Previous research showed that pediatric low-grade gliomas contain gene mutations that increase the activity of two cell signaling pathways: mammalian target of rapamycin complexes 1 and 2 (mTORC1/2) and Ras/mitogen-activated protein kinase (MAPK), says Raabe. Both enable proteins that promote cell growth.
TAK228/sapanisertib, which is in clinical trials for adult patients with cancer, inhibits the mTOR pathway; trametinib, which is approved for treatment of melanoma, inhibits the MAPK pathway.
When Raabe and team treated tumors or cells with just one of the drugs targeting one of the pathways, the cancer cells were able to use the other pathway to survive, Raabe says.
In the new study, Raabe and colleagues tested TAK228 and trametinib in patient-derived pediatric low-grade glioma cell lines grown in the laboratory. Using the two drugs together led to a 50% reduction in tumor cell growth.
The combination therapy also suppressed activity by more than 50% in both the mTOR and MAPK signaling pathways, and reduced cell proliferation by more than 90%.
The combination killed some pediatric low grade glioma cells — increasing the cells killed by nearly threefold over cells treated with each agent alone.
The investigators then gave mice implanted with human low grade glioma tumors TAK228, trametinib, the combination of the two drugs, or a combination placebo. Survival was three times longer in the animals receiving the combination therapy versus single treatments, a difference of 36 days compared with 12 days.
Combination therapy-treated tumors were 50% smaller on average over two weeks' treatment time compared with single drug therapy. Combination therapy in the animal models led to suppressed mTOR and MAPK pathways by more than 80%. The number of growing cells in these tumors decreased by more than 60%.
The blood supply to the tumors was decreased by 50%-95%.
Raabe cautions that more preclinical research must be done to determine the best and safest potential dosing regimen, in part because trametinib stays in the body for four to five days, and the MAPK pathway it targets is needed by healthy cells for normal growth in children.
In addition, mice receiving the combination therapy didn't grow as well as those receiving single drug therapy, so the dosing schedule needs to be customized for children, he says.
Currently, TAK228 is in clinical trials in adults, and early phase clinical trials of TAK228 are being considered for pediatric brain tumors, Raabe says.
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My Husband Died From Brain Cancer. Johns Hopkins Medicine Should Be Ashamed, Not Me
Jul 22, 2016 · 7 min read
On May 27, 2015, my brilliant and beloved 58-year old husband, Bruce Israel died from brain cancer that had been diagnosed a scant ten months earlier — scarcely three-weeks after a return from an overseas family vacation to celebrate our older daughter’s high school graduation.
The discovery of my husband’s tumor — lodged deep in his mid-brain stem — was heralded by a week of mysterious double vision, blazing headaches, vertigo and eventually loss of speech -all signs of severe hydrocephalus that caused by the three-centimeter mass blocking his third ventricle.
Because the tumor presented itself with heightened urgency — a shunt was needed to drain excess fluid and staunch the swelling in my husband’s brain — there was no time to do anything but locate a skilled neurosurgeon who wasn’t on vacation and could operate without delay.
The shunt successfully abated my husband’s symptoms, but the biopsy, which was also part of the surgery also revealed an aggressive glioma that couldn’t be removed, only treated.
By that time, about a week had passed since my husband’s diagnosis, and I was still in a state of panic; trying to absorb the news that my husband’s life would be cut brutally short, while figuring out how to find the time to care for my husband while doubling my law firm’s revenue to replace my husband’s lost income, getting my daughter up to college for the start of her freshman year the following week. So while I did some online research to get an overview of the brain cancer terrain, I just couldn’t find the time for exhaustive research or the resources to fly my husband around the country in search of top experts. Instead, I settled on the proverbial boy next door — Johns Hopkins Medicine — an institution that holds itself out on its website as a leader in advanced brain cancer treatment, that garnered glowing reviews from area doctors, that could treat my husband at convenient local outposts at Sibley and Suburban Hospital, a few miles from our home — and that ultimately, utterly and completely failed my husband on so many levels.
Among other things, Johns Hopkins Medicine relied on its own, rudimentary in-house tests to evaluate the tumor’s pathology rather than FDA-approved procedures that are more granular and would have identified critical biomarkers.
In turn, this information would have informed my husband’s diagnosis and treatment, since biomarkers can predict the ly success of radiation and chemotherapy.
the information that I’ve managed to piece together since my husband’s death, it was fairly ly at the outset that neither radiation nor chemo would have much success against his tumor (an outcome corroborated by the actual clinical results).
Had Hopkins gathered and used this information as a basis for treatment, I would have pressed for other emerging treatments (such as the Optune Cap), Avastin or other measures more suitable for his genetic makeup. Instead, the radiation and chemo that he was subjected to took a toll on his cognitive ability and weakened him and hastened his demise.
Johns Hopkins also promised, but never delivered “Hopkins-caliber” treatment at locations Sibley and Suburban hopsitals convenient to our home.
But what Hopkins never told us is that my husband’s Hopkins neuro-oncologist, based the Baltimore mothership and most familiar with its procedures, would be hamstrung in his ability to treat my husband onsite at Sibley, when he couldn’t seamlessly order MRIs or view certain records.
Nor did Hopkins tell us that our neuro-oncologists’ schedulers at Sibley lacked access to his calendar in Baltimore; when my husband’s health declined precipitously and I begged the scheduler for an appointment with our neuro-oncologist in Baltimore, she was unable to make it happen.
Worst of all, when I had no choice but to bring my husband to the emergency room at the Hopkins hospital where my husband had his original surgery, his neuro-oncologist could not even visit or treat him there because Hopkins had not, and would not grant him privileges at Suburban, a Hopkins-owned facility.
As a result, I spent the final ten days of my husband’s life pleading (unsuccessfully) with a palliative care doctor who didn’t feel that any additional treatment was appropriate instead of having the ability to devise a plan with his neuro-oncologist.
Of course, I tried to voice my concerns during my husband’s treatment at Johns Hopkins. I emailed relentlessly, including six emails and two phone calls to patient relations that went unanswered.
I tried again to reach out to the Johns Hopkins Patient Advocate three more times after my husband’s death just for a sense of closure.
Yet after all this time, no one from Hopkins has either explained or apologized why my complaints went unaddressed and why my husband’s neuro-oncologist was denied privileges.
In the almost fourteen months since my husband’s passing, I’ve not shared my full experience publicly. My silence stemmed partly concern for my family’s privacy but largely because of my own feelings of embarrassment and shame at not having done more.
Despite having excellent (and costly) health insurance coverage, I felt ashamed that I wasn’t able to secure better care for my husband.
And despite considering myself a highly educated and resourceful person, I felt ashamed for not having really hunkered down and committed myself to understanding the medical literature and chasing experts in search of better treatment as others have successfully done.
wise, while I advocated for my husband, I didn’t go far enough. I felt ashamed that I never had one of those “Shirley McLaine/Terms of Endearment moments where she screams and shrieks at the nurses until they deliver pain medication to her cancer-ridden daughter played by Debra Winger.
Sure, I sent emails, I made phone calls but I should have planted myself outside my husband’s hospital room and demanded that Hopkins permit my husband’s Hopkins neuro-oncologist visit and treat my husband at a Hopkins-owned hospital.
For fifteen months, I’ve lived with this embarrassment and shame. The shame rears its head in recurring dreams, where I see myself reaching back, desperately clutching at my husband’s hospital gown to pull myself back to him and to a point where I could do things differently.
The shame taunts me each time I read of a new advancement in brain cancer that my husband might have availed himself of if he’d have lived just a few months longer.
Most of all, the shame catches in my throat and chokes me up each time I reminisce about my marriage and how my husband had my back in every single way and yet I didn’t have his at a time when he needed me most.
Fifteen months is a long time to labor under the weight of shame — but it’s also enough time for the light of reason to poke through. And what I’ve realized is (duh!) that I have no reason to be ashamed; instead, it’s Johns Hopkins Medical that should be ashamed of itself.
Maybe I could have interviewed more experts before settling on Johns Hopkins for treatment.
But I certainly didn’t do anything wrong or act imprudently by putting my husband’s care in the hands of a hospital that boasts about its expertise and cutting edge brain cancer treatment on its web page.
Maybe I should have educated myself more extensively on on brain tumor molecular markers and their role in prognosis, but I’m not a doctor or a cancer researcher.
Instead, it was Johns Hopkins’ Medicine’s job to use FDA-approved tests for biomarkers that are the standard of care at places MD Anderson and Sloan Kettering and the numerous other bonafide cancer treatment centers around the county.
And yes, maybe I should have pulled a Shirley McClaine and screamed my head off until Johns Hopkins would allow my neuro-oncologist privileges to visit my husband at the hospital.
But I shouldn’t have had to throw a tantrum when to persuade a medical facility that lured my husband for treatment with promises of “convenient care” to grant one of its own doctors privileges at one of its own hospitals to treat one of its own patients.
Moreover, even though my husband had terminal brain cancer and his life would certainly be cut short, I am not embarrassed or ashamed or somehow in denial to have expected better treatment than we received.
Even though my husband wasn’t expected to live long, that didn’t give Johns Hopkins the right to give up on him without even trying.
That’s particularly true at a time when medicine is advancing at the speed of light, and extending a patients’ life by even three or four months can give them access to treatments that weren’t available before.
Had my husband lived another month, he could have easily accessed the Optune cap which by then, had been FDA approved. Or he might have been able to qualify for laser ablation , a minimally invasive surgery that might have debulked his otherwise inoperable tumor.
Fourteen months later, I finally realize that I did not fail my husband, Johns Hopkins Medicine did.
What’s more, I also realize that establishments Johns Hopkins and other medical providers count on our shame to keep us silent so that they can evade accountability for their malfeasance.
So hear this, Johns Hopkins Medicine: my husband died in your care, you should be ashamed of yourself. I will not be silent any longer.
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Brain Tumors: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Johns Hopkins is one of the leading research and treatment centers in the world for brain tumors. At the Brain Tumor Center, experts from all specialties coordinate patient care and develop innovative treatments and clinical trials.
Brain Tumor Experts
Our brain tumor experts lead the nation's research and continue to set standards for cancer care. Multidisciplinary care teams bring individualized approaches to each patient and unparalleled experience in delivering care.
About Brain Cancer
Until recently, little progress has been made in controlling this disease. One of the first breakthroughs in brain cancer treatment in 25 years — the use of implantable wafers to deliver chemotherapy directly to the tumor site — was developed at Johns Hopkins.
Our physicians also employ new brain imaging technology not available elsewhere in the region to make an accurate diagnosis leading to precise treatment. Cancer found in the brain that started somewhere else in the body and spread to the brain is called brain metastasis.
Brain tumor specialists work together to diagnose the patient's type of cancer and the stage of disease. New technologies have produced breakthroughs in obtaining the crucial information.
An imaging technique called WAND was developed by NASA but adapted for brain tumor diagnosis at the Kimmel Cancer Center. This technology enables the physician to “see” tumors in the skull in 3-D in real time and to pinpoint the cancer.
The mathematical coordinates are used in the operating room computers to provide a blueprint for preserving surrounding tissue, thereby minimizing complications.
Additional information gathered from positron emission tomography (PET) scans can be combined with the 3-D data to differentiate a stroke from brain cancer and to determine who needs surgery and who does not. Roughly 25 percent of patients referred for brain cancer surgery are told they do not need surgery.
Please see a doctor if you experience any of the following symptoms: frequent headaches, vomiting, or difficulty walking or speaking.
In addition to surgery, the treatment of brain tumors often requires radiotherapy and/or chemotherapy treatments.
Brain tumor patients at the Kimmel Cancer Center and Brain Tumor Center have access to many promising new therapies before they become widely available, and many new drugs for brain tumor treatment are developed and studied here.
Radiation therapy is delivered by special 3-D imaging techniques, and minimally invasive stereotactic radiosurgery can be used when appropriate.
One challenge in treating cancer is being able to deliver chemotherapy to the site of the tumor, avoiding general drug treatments that may affect healthy tissue.
For some patients at Johns Hopkins, a polymer wafer is left behind after brain surgery. This wafer emits a regular dose of chemotherapy that attacks only the cancer.
This wafer has proven effective in shrinking brain tumors that responded to no other treatment.
The Johns Hopkins Metastatic Brain Tumor Center coordinates care for patients with metastatic tumors to the brain (tumors that begin elsewhere but spread to the brain).
New Treatment Approaches
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins plays a leading role in the search for cancer-fighting drugs.
For example, we have directed a six-hospital study funded by the National Cancer Institute to investigate the effectiveness of Taxol, a breast cancer drug, and suramin, a drug first used to fight prostate cancer, in treating brain cancer.
Along with other institutions across the country, the Kimmel Cancer Center is a member of the Adult Brain Tumor Consortium (ABTC). ABTC is a National Cancer Institute-funded group that collaborates on Phase I and II evaluations of promising therapies for primary central nervous system cancers.
Cytomegalovirus (CMV) Research
Johns Hopkins scientists are conducting research in high-grade glioma patients to measure the blood levels of cytomegalovirus (CMV), a common virus that can cause severe disease in patients with weakened immune systems.
Glioma patients can experience weakened immune systems as a result of therapies radiation, chemotherapy and high-dose steroids used to treat their cancer.
The scientists will analyze whether blood levels of CMV in high-grade glioma patients currently receiving standard therapies correlate with changes in blood counts, an indicator of a therapy’s success or failure.
Ultimately, the Johns Hopkins investigators hope to determine whether high-grade glioma patients should be routinely screened for CMV and if antiviral medications or treatment may have an impact on outcomes. Learn more and support this research.
Brain Cancer Survivorship
Brain cancer survivors should allow extra time to recover — your body and brain need time to heal after treatment. You may have permanent scars or hair loss, and you may not be able to resume your lifestyle activities at the same pace.
Side effects of treatment may linger for months or years. You may have residual side effects including headaches, motor and sensory loss, fatigue, and difficulty with memory, speech or cognition.
Always discuss any health concerns and symptoms with your doctor.
Brain tumor patients have difficulty with cognition for several reasons: the brain is taxed by the tumor, surgery, medications, radiation, and chemotherapy all in a short time.
Writing down lists or tasks, or placing signs around your home reminding you to do things lock the door and when to take your medications, can help. Ask friends or family members to help out with tasks balancing your checkbook that might seem difficult.
Your doctor or nurse can give you advice, or refer you to occupational and speech therapists for additional support if necessary.
As you recover, take charge of your health by eating healthy, exercising and reducing stress. Avoid tobacco and limit alcohol intake. Keep up with screenings for other cancers, mammograms and colonoscopies.
The Johns Hopkins Comprehensive Brain Tumor Center is one of the largest brain tumor treatment and research centers in the world.
Experts there treat an extremely large number of patients affected by all types of brain tumors and tailor the best, most advanced therapies that each unique tumor demands. There are many useful organizations to help, too.
The American Brain Tumor Association to has information on brain tumor research and support groups, and a section for caregivers. The Healing Exchange Brain Trust runs a number of online support groups.
Could Canine Patients Help Find A Cure For One Of The Deadliest Cancers?
BALTIMORE (WJZ) — Glioblastoma is a very aggressive form of brain cancer that’s usually fatal.
It’s the type of cancer that plagued late senators John McCain and Edward Kennedy as well as Beau Biden, the late son of former Vice President Joe Biden. But scientists are hoping man’s best friend can help find a cure for men — and women — diagnosed with glioblastoma.
Johns Hopkins Sidney Kimmel Cancer Center was recently given funding to research a new experimental treatment on dogs who’ve been diagnosed with brain cancer — in hopes that the treatment will ultimately save humans.
What Is Glioblastoma? How Scientists Are Working To Cure This Aggressive Form Of Cancer
It combines heat and radiation to directly destroy cancer cells and the hope is, if it works in canines it can then be tested on humans.
Belle, a beautiful 9-year-old shepherd, was very recently diagnosed with a brain tumor.
Veterinarian Dara Kraitchman, a professor in the Johns Hopkins Medicine Department of Radiology and Radiological Science, diagnosed Belle using an MRI after the dog began having seizures. Right now, there’s very little that can be done to save her life other than invasive surgery that often kills the animal it’s attempting to cure.
“No one wants their pet to be in pain — with surgery, there’s always pain,” Kraitchman said.
“It would be nice if we could communicate with the dog and we knew what the dog really thought, but we don’t have that,” said Belle’s owner Charles Cummings, a nose and throat oncologist at Hopkins.
So, Belle’s owners have decided not to try surgery and there’s little else that can be done. But, scientists are hoping that there will be in the future.
A team of scientists from the Kimmel Cancer Center have been working for more than five years developing a technique that they hope could, in the future, save Belle and other dogs with cancerous brain tumors. It uses iron oxide nanoparticles.
A nanoparticle is a little over a millionth times smaller than a cell — a human cell.
Dr. Robert Iov has developed a way to take an iron oxide nanoparticle, inject it into a tumor and then heat it using a magnetic field. He created this machine where, so far, they’re experimenting on mice.
“The nanoparticles, if we’ve already injected them into the tumor — the mouse will go inside here and then we apply the magnetic field to treat the tumor,” said Iov.
The key is to control the heat using probes he developed because, as he demonstrated with a screwdriver, the coils create a powerful magnetic field.
“The screwdriver basically went from room temperature to a couple of thousands of degrees in a matter of seconds,” Iov said.
Once heated, the tumor is then directly radiated. The combination of heat and radiation has long been known to damage cancer cells.
“The problem we had before was it was very difficult to heat an individual part of the brain and not injure the person. You have to heat large areas,” said Hopkins radiation oncologist Dr. Lawrence R. Kleinberg said.
Denise Koch: Sounds you’re very hopeful about this new treatment?
Dr. Kleinberg: These nanoparticles can be given right to the tumor and so we can heat just the area we should be heating while the radiation is given.
Kleinberg is a part of the team that will treat canine patients using an MRI machine the ones used on humans.
“Inside the brain, no matter what we do we’ve been unable to cure very many people at all and that’s the reason a break-through would be very exciting,” he said.
Iov has built a second machine for canine patients, dogs whose owners decide because of an otherwise terminal diagnosis, they want to be part of this clinical study.
“What we learn in the dogs we can then translate to humans,” Iov said.
Unfortunately for Belle, she won’t even have the option for this treatment.
“If this was a 3-year-old dog, I think we would consider very strongly doing the protocol,” said Cummings, Belle’s owner. “Because she’s a 9-year-old dog, and shepherds don’t have a life span more than 9 or 10 years, that comes into the decision-making process for us.”
While Belle’s family decide she’s simply too old to go through this protocol, it could offer real hope for other pet owners whose dogs get this difficult diagnosis.
“This is kind of nice because we’re going to do it first in pets and then, if people are lucky, they’ll get the same treatment, too,” said Dr. Kraitchman.
The team at Hopkins is hoping to research the nanoparticle treatment on five or six dogs. If your pet is diagnosed with a brain tumor and you want to try this treatment, reach out to the Johns Hopkins Sidney Kimmel Cancer Center.
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Jon Weingart, MD, discusses what a “multidisciplinary” approach to brain tumor treatment means? Dr Weingart is a neurosurgeon and professor of Neurological Surgery and Oncology at Johns Hopkins Medicine.
Treatment for patients with brain tumors is best developed by a multi-disciplinary team that includes tumor physicians from various medical specialties, including but not limited to neurosurgeons, neuro-oncologists, radiation therapists, and pathologists. Learn more about our team below:
Professor of Neurosurgery Professor of Oncology Jennison and Novak Families Professor of Neurosurgery Director, Meningioma Center Professor of Neurosurgery Joint Appointment in Ophthalmology Professor of Biomedical Engineering Professor of Oncology Director, Department of Neurosurgery Harvey Cushing Professor of Neurosurgery Neurosurgeon-in-Chief, The Johns Hopkins Hospital Director, Hunterian Neurosurgical Research Laboratory Co-Director, Brain Cancer Program, Sidney Kimmel Cancer Center Associate Professor of Neurosurgery Associate Professor of Oncology Associate Professor of Otolaryngology – Head and Neck Surgery Director of the Neurosurgery Skull Base Center Director of Endoscopic and Minimally Invasive Neurosurgery Director of the Pituitary Center Professor of Neurosurgery Vice Chair of Neurosurgery, Johns Hopkins University School of Medicine Director, Department of Neurosurgery, Johns Hopkins Bayview Medical Center Director of Cerebrovascular Neurosurgery, Johns Hopkins Bayview Medical Center Director, Neurosurgery Residency Program Director, Cerebrovascular Neurosurgery Fellowship Program Co-Director, Multidisciplinary Adult Cranioplasty Center Co-Director, Chiari Center Professor of Neurosurgery Professor of Oncology Professor of Otolaryngology – Head and Neck Surgery Professor of Radiation Oncology and Molecular Radiation Sciences Director of Brain Tumor Immunotherapy Director of the Metastatic Brain Tumor Center Director of the Johns Hopkins Trigeminal Neuralgia Center Assistant Professor of Neurosurgery Assistant Professor of Neuroscience Assistant Professor of Otolaryngology – Head and Neck Surgery Division Chief of Johns Hopkins Neurosurgery, National Capital Region Chief of Neurosurgery, Johns Hopkins Suburban Hospital Assistant Professor of Neurosurgery Assistant Professor of Oncology Assistant Professor of Radiation Oncology and Molecular Radiation Sciences Director of Neurosurgical Oncology, Johns Hopkins Bayview Medical Center Professor of Neurosurgery Professor of Otolaryngology – Head and Neck Surgery Walter E. Dandy Professor of Neurosurgery Director, Division of Cerebrovascular Neurosurgery Vice-Chairman, Department of Neurosurgery Neurosurgical Co-Director, Neurosciences Critical Care Unit Professor of Neurosurgery Professor of Oncology Director, Neurosurgical Operating Room
Professor of Neurology Professor of Neurosurgery Professor of Oncology Director, The Johns Hopkins Comprehensive Neurofibromatosis Center Professor of Neurology Professor of Neuroscience Professor of Oncology Co-Director, Brain Cancer Program, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Director, Division of Neuro-Oncology
Professor of Oncology Professor of Medicine Professor of Neurosurgery Co-Director, Brain Cancer Research Program, Sidney Kimmel Cancer Center Associate Professor of Oncology Associate Professor of Neurosurgery Joint Appointment in Medicine
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