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Pushing the Boundaries for Brain Tumor Treatment

Surgical neuro-oncologist Rohan Ramakrishna, MD, and his colleagues at the Weill Cornell Brain and Spine Center are pushing the boundaries of treatment for patients with gliomas, metastatic disease, skull base lesions, and pituitary disorders, employing the newest techniques and technologies available. These include awake mapping, imaging techniques, and microsurgery to ensure maximal tumor removal and achieve the safest surgical outcomes.

“A number of significant therapeutic advances have emerged for the treatment of brain tumors in just the last year,” says Dr. Ramakrishna, Director of the Brain Metastases Clinic at Weill Cornell Medicine. “One area we are particularly excited about is the use of high-intensity focused ultrasound [HIFU] for the treatment of deep subcortical tumors. Maintaining quality of life is one of our primary goals in brain tumor surgery. Oftentimes, these subcortical tumors are not accessed for the purpose of total removal using traditional means because of the potential for collateral neurologic damage. Typically, we are forced either to do a limited biopsy or treat those lesions with laser therapy or radiosurgery, and all of those alternatives have some drawbacks.”

Dr. Rohan Ramakrishna

Dr. Rohan Ramakrishna

High-intensity focused ultrasound therapy, pioneered by neurosurgeon Michael G. Kaplitt, MD, PhD, Director of the Weill Cornell Brain and Spine Center, enables a surgeon to lesion the abnormally functioning area of the brain completely noninvasively with MR thermometry. In 2016, the FDA approved its use for the treatment of essential tremor.

Dr. Ramakrishna and Dr. Kaplitt are currently collaborating to pilot this technique for patients with gliomas and other subcortical tumors. “We know that total or near total removal of the glioma results in better patient outcomes from the standpoint of survival and responsiveness to other therapies, such as chemotherapy and radiation,” says Dr. Ramakrishna. “Ideally you want to try and remove as much tumor as you can prior to starting the journey with these other therapies. With this new technology we have the ability to ablate the entire tumor noninvasively in a conformal way, providing the same benefit as removal without the collateral neurologic deficit.” Their study proposal is currently under IRB review; the physicians hope to begin using this approach for subcortical tumors in the spring.

Weill Cornell physicians are also using ultrasound experimentally in the laboratory to disrupt the blood-brain barrier. “Most chemotherapies do not get into the brain effectively. By using ultrasound technology, we can temporarily disrupt the blood-brain barrier so that chemotherapies are now potentially in play for patients with these hard-to-treat tumors,” says Dr. Ramakrishna. “This approach may someday obviate the need for convection-enhanced delivery. We’re currently putting together a clinical trial for this purpose and expect it to begin in early 2019.”

Weill Cornell is also participating in the ongoing DNAtrix clinical trial that is using oncolytic virus immunotherapies for patients with either a first of second recurrence of glioblastoma for whom surgery is not possible or planned. “In this trial we inject a modified cold virus into the tumor and then follow that injection with immunotherapy. We don’t have the results yet, but so far the trial is going well and remains open,” says Dr. Ramakrishna, adding that discussions are underway to expand the viral oncolytic trials therapy portfolio to include patients with newly diagnosed glioblastoma.

“Another area where we are pushing boundaries pertains to minimally invasive access to skull base tumors using endoscopes to obtain biopsies,” adds Dr. Ramakrishna. In a paper published in the Journal of Neuro-Oncology in November 2018, Weill Cornell investigators assessed the use of a tubular retractor-based minimally invasive biopsy technique to provide improved tissue yield. “We found doing the biopsy in this way is equally as safe as needle biopsies, but also enables us to obtain much more tissue for genomic profiling testing that we consider standard of care today.”

A Successful Surgery...and Then Some

Dr. Rohan Ramakrishna and the neurosurgeons at the Weill Cornell Brain and Spine Center share expertise in the treatment of meningioma, the most common, yet often complex, benign intracranial tumor that, if left undetected, can be severely disabling and life-threatening. Slow-growing benign tumors can also cause increasing symptoms as they progress, including hearing loss, which Maria Silver began to experience two years ago. The retired teacher, now 67, realized she wasn’t hearing well and saw an otolaryngologist, who ordered an MRI that revealed a large frontal meningioma. Other changes that she’d previously attributed to aging – slower thought processes, incontinence, and sometimes slurred speech – now made sense.

Researching neurosurgeons, Ms. Silver and her husband found Dr. Ramakrishna. “I felt very comfortable with him,” she says. “He was knowledgeable and reassuring. He told me what the surgery would entail, and we made the appointment for the surgery.”

Maria Silver

Maria Silver

Dr. Ramakrishna safely removed the tumor while reconstructing Ms. Silver’s skull to maintain a normal shape. When she awoke from surgery, all of her symptoms were gone, with one unexpected but very welcome side effect. Color-blind since birth, she looked out the window at the East River in awe. “I was looking at all the different colors that I had never seen before,” she says. “It was a miracle. I could not believe it.”

Dr. Ramakrishna is thrilled that his patient not only did so well in surgery, but also got an amazing bonus. “I can’t say that I fully understand it,” he says, “because it doesn’t make sense medically that the surgery would have affected Maria’s ability to see color. The tumor wasn’t near the optic nerve or the occipital lobe, so it shouldn’t have had anything to do with vision at all, let alone color vision. But I’ll take it!”