Clinical immunotherapy application in metastatic glioblastoma
Mentor: Annick D. Van den Abbeele, MD, FACR (Dana-Farber Cancer Institute)
Glioblastoma multiforme (GBM) is an aggressive brain tumor that arises from astrocytes, a type of supportive glia found in the brain. Glioblastomas typically have extensive finger-like vasculature growing beyond the initial neoplasm, making it hard to surgically remove the entire tumor. The median survival rate for a typical GBM patient is about 14 months with current treatment options including a combination of the following: surgery, radiotherapy, and chemotherapy. The purpose of this study is to use novel therapeutics, specifically genetic immunotherapy, to investigate whether using a person’s immune system can increase the quality of life and offer maximum survival benefits. Immunotherapy targets a patient’s own immune cells, specifically a protein on T cells called PD-1. When PD-1 binds to proteins like PD-L1 and PD-L2 (found on cancer cells), the cancer cells can turn the immune cells off, allowing the tumor to spread and multiply without interference. By blocking PD-1, the body can reactivate immune cells that the tumor may have deactivated, which will allow immune cells to do their job and attack cancer cells. This can both help shrink the tumor as well as prevent it from continuing to grow. In this experiment, patients will receive one of 3 doses of an anti-PD1 drug along with an monthly MRI to assess progress as compared to baseline. Using T2 weighted FLAIR and post-contrast MRIs, neoplasm progression can be assessed by measuring the apparent diffusion coefficient (ADC) in DWI imaging and the relative cerebral blood volume (rCBV) in DSC imaging. Because the average rCBV is much higher in tumors than normal brain matter, pseudoprogression can be analyzed by comparing the site in question to the patients’ gray matter and analyzing the difference in cerebral blood volume. This allows for accurate estimations of pseudoprogression without invasive methods like surgery, and can highly influence treatment decisions. By calculating the ADC and rCBV of the brain tumors, the study seeks to compare the size, vasculature, amount of necrosis, and pseudoprogression of the neoplasm in comparison with other sequential scans in the same patient over the course of treatment. By analyzing the tumor regularly using DWI and DSC MR imaging, the grade, stage, and progression can be assessed and the prognosis and efficacy of the treatment can be determined and altered to provide the longest OS possible.
The immune system can be turned on to recognize cancer cells by modifying a patient's cells to produce antibodies that bind tumor cells and are recognized by T-cells as foreign. Source: http://cancergrace.org/lung/tag/anti-pd-l1/ Source: