MRI-guided radiotherapy for glioblastoma and spinal bone metastases

Glioblastoma is the most common cancer originating in the brain with ~12,000 new diagnoses per year in the U.S.A. and median survival about 18 months. A common dilemma for the patient and treatment team is that the clinical MRI one month after radiation therapy shows growth of unclear significance in up to 50% of patients. Patients with true progression of non-responding tumor continue to progress on serial MRIs and usually die within 9 months. True progression is usually determined 6 or more months after completion of radiotherapy, often when it is too late to intervene. Our goal is to identify glioblastoma patients with true progression early during treatment and implement aggressive second-line therapy to improve survival. Our innovative approach to identify early progression uses neuroimaging and image processing on MRIdian, a new combination MRI and radiotherapy device where patients undergo MRI daily as part of their radiotherapy. Our preliminary data with MRIdian is the first to demonstrate daily glioblastoma growth on MRI in patients during radiotherapy. By developing physiologic MRI techniques on MRIdian, we seek to identify when there is growth during treatment and intensity treatment to those patients. We also investigate tissue and blood based biomarkers that will help us to make these predictions of response during treatment.

In the spine, surgery is an effective treatment to alleviate the symptoms of metastatic epidural spinal cord compression. However, patients frequently have radiographic evidence of cord abutment or compression without significant neurologic compromise. In these asymptomatic patients, can surgery be avoided? MRIdian can account for spinal cord and tumor size and position in real-time before and during radiation therapy. We use weekly (or “pulsed”) MRI-guided precisely focused radiation to create a non-invasive “separation surgery”. By targeting tumor at progressively increased distance from the spinal cord week to week and fraction to fraction, pulsed MRI-guided adaptive replanning can further reduce risk of radiation myelopathy and improve target coverage without need for surgery.

Improved Whole-Brain Spectroscopic MRI for Radiation Therapy Planning and Response Prediction

Identifying the extent of brain tumor margins for radiation treatment planning remains a challenging task due to the infiltrative nature of glioblastoma. Multiple studies including our own have demonstrated that an MR technique for detecting metabolites in tissue, MR spectroscopic imaging or spectroscopic MRI (sMRI), can detect areas of infiltrating tumor with a high degree of sensitivity and specificity, enabling better radiation treatment of areas that lead to early recurrence and extending life. sMRI enables the identification of tumor extent that is marked by increased Choline/N-Acetylaspartate ratios, including regions that are not detectable by diagnostic MRI and that are normally left untreated. By allowing these previously undetected regions to be treated, sMRI has the potential to improve the efficacy of radiation treatment and significantly delay recurrence. In our 3-site sMRI-guided radiation dose escalation pilot study which was completed in 2019, we were able to demonstrate feasibility and safety. Survival analysis of all 30 GBM patients shows a promising median overall survival (OS) of 23 months compared to 16 months OS for GBM patients receiving standard-of-care. We are currently promoting further clinical trials with this technique in brain cancers and using the sMRI to predict early cancer response to therapy.

Nevertheless, approximately 80% of GBMs eventually recur locally. Current treatment options for recurrent GBM (rGBM) include second resection, repeat radiation (re-RT), and systemic therapies to limit tumor regrowth. However, a major limitation of rGBM imaging is that active rGBM is difficult to distinguish from benign or first-line therapy related changes (e.g. leukoencephalopathy, RT necrosis, etc) leading to omission or overly conservative application of re-RT and surgery. Given the confusing imaging results in rGBM, we propose that sMRI will be even more useful to guide second surgery and re-RT and increase their effectiveness. We are also investigating the usefulness of sMRI in surgery, radiation planning, and response prediction in other brain cancer types.