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Neurology and Neurosurgery

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Basic and Translational Science Projects

Circulating Tumor DNA As an Early Marker of Radiation Response in an Animal Model of Spine Metastases

Principal Investigators: Daniel M. Sciubba and Chetan Bettegowda

Not all tumors are radiation sensitive and, unfortunately, a patient may have completed the regimen by the time that is learned. A potential new technology to determine if radiation treatment is effective involves measurement of circulating tumor DNA (ctDNA), which is found in many kinds of cancer. In our model, we will implant human tumors into the spines of rats and then treat them with focused radiation. Levels of ctDNA will be measured before and after radiation to see if they correspond to cancer cell death. If shown to be good markers, changes in ctDNA levels could be used by care providers to: 1) learn if radiation is effectively treating the cancer and 2) change or discontinue the radiation treatment plan.

Chemotherapeutic and Radiographic Interventions in the Treatment of Primary and Recurrent Chordoma

Principal Investigator: Daniel M. Sciubba

Currently, the gold standard for chordoma care is complete resection, combined with radiation administered either before or after surgery. However, radiation can often prevent proper fusion of the spinal hardware. Additionally, no good chemotherapeutic drugs have been identified for treatment of chordoma. As a result, we seek to identify both chemotherapeutic regimens and optimal radiation timing in an animal model of chordoma, with the hope that such work can lead to clinical trials and improvements in the treatment of spinal and sacral chordoma.

Our previous work to this end has included creating an animal model of chordoma that replicates the disease’s radiographic, behavioral and neurological features (source). We are now hoping to begin the next phase of the project, which uses this model to address the previously mentioned endpoints.

Effect of Laminectomy Method on Post-Decompression Osteonecrosis

Principal Investigator: Daniel Sciubba

Funding: Stryker Corporation

Laminectomy is considered the gold standard for surgical decompression of the spinal cord, helping treat multiple conditions including spinal stenosis, intervertebral disc herniation, oncologic neural element compression and spinal trauma with posterior bone fragment displacement.

However, surgical decompression is not without risks. Patients may experience iatrogenic neural element injury, residual postoperative pain (often secondary to disruption of the posterior tension band), progressive deformity requiring surgical revision, infection and wound dehiscence. Additionally, even in cases without incidental injury, direct trauma to the bone and cartilage at the surgical site during decompression results in edema and necrosis of the local tissues. In addition to increasing risk of persistent paraxial pain, such necrosis may create a local tissue environment that is unfavorable for bony fusion, increasing the risk of nonunion (pseudoarthrosis) and the need for revision surgery.

Currently, surgeons use either traditional rongeurs (Leksell + Kerrison) or ultrasonic cutting tools to perform laminectomies at the site of weight drop and lumbar drain placement. One of the touted merits of the ultrasonic cutting device is its ability to make cleaner osteotomies through the lamina, thereby potentially reducing local tissue damage during surgery.

Despite this claim, current literature is limited regarding the relative damage that each type of device imparts to the bony tissues.

Cysteamine As Inhibitor of Breast Cancer Spinal Metastasis in Mice

Principal Investigator: Daniel M. Sciubba

One of the most common sites of breast cancer metastases is the axial skeleton, leading to significant pain and a decrease in quality of life. Triple-negative breast cancer carries a particularly poor prognosis, with a median survival time of 6.7 months compared to 22.4 months for patients with receptor-positive tumors. Unlike hormone-responsive tumors, triple-negative disease has few good options for systemic therapy and often leads to rapid metastatic spread.

Given the difficulties of gaining Food and Drug Administration (FDA) approval for new medications, we also seek to identify agents with demonstrated safety and prior governmental approval.

Cysteamine is FDA approved for treatment of nephropathic cystinosis, and has shown a great safety profile in humans as young as 2 years old. Preliminary in vitro data has also suggested that cysteamine can block the metastatic spread of triple-negative breast cancer. If successful, the evidence provided by this investigation could be used to support early phase clinical trials.

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For more information on clinical projects at the Johns Hopkins Neurosurgery Spinal Research Lab, please call us at 410-502-6103.

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