Advances in brain cancer treatments, to an outsider, look a lot like watching a snail race. Identifying either a cure or a means of making something like a GBM (Glioblastoma) or a DIPG (diffuse intrinsic pontine glioma) manageable, seems like a long way off, particularly if one knows someone given such a diagnosis. And yet, researchers throughout the world continue to collaborate and tweak models in the hope of either extending life beyond current medical practices or finding a cure altogether. Last summer, we reported on some research conducted by the NIH, specifically CED (Convection Enhanced Delivery) in developing potential treatments (or means of managing) these types of diagnoses. So lo and behold, as I have spent the last 10 days touring Israel with my family on holiday, a simple Google search uncovered a pair of CED researchers (to clarify, one is a nuclear physicist and the other a neuro-surgeon) who kindly sat down with us to explain the challenges behind CED and why it offers a hope for the future not only for brain cancer patients but other “white matter ailments.
Yael Mardor, a nuclear physicist by training with an MRI imaging background and Zvi Ram a neurosurgeon who studied under Edward Oldfield at the NIH, partnered over ten years ago to begin using advanced imaging for CED procedures to specifically address a population of individuals with recurrent glioblastomas (GBMs) (this the type of brain tumor that took Senator Ted Kennedy’s life). GBMs represent the most malignant type of brain tumor and individuals diagnosed with these tend to have a life expectancy of about one year. Surgery serves as one option and most hospitals use a combination of radiation plus chemotherapy but the tumor typically reappears after three months. Recurrent tumors tend to respond to very little by way of medical intervention. This became the target audience for Mardor and Ram because current medical treatments offered little to no help and those that face a recurring tumor tend to become the first target for new experiments that can be dangerous.
Initially, the Israeli team didn’t know how to image the CED process. Think of throwing a dart at a dartboard. One wouldn’t dream of trying blindfolded. Imaging is to the CED process what hand/eye coordination is to one’s dart game. In CED, the process of infusing a drug into the effected area becomes mission critical miss the key spots on the tumor and the drugs don’t “infuse. In addition, the “imaging aspect of the process allows the team to continuously monitor toxicity. Imaging provides for immediate analysis, unlike traditional chemotherapy methods, for example in which the results “get reviewed but at much longer intervals. Because “where the drug gets delivered and how much gets delivered plays such a crucial role in terms of the effectiveness of not only the drug infusion, but also how the tumor responds to the infusion. Imaging has become the critical element of the entire process.
The Israeli team relies upon gadolinium as a contrasting agent for the MRI process (iron oxide can also work though instead of creating a “white image it generates a “black image or hole). We should re-state the rationale behind CED. Because of the blood-brain barrier, traditional intravenous drug delivery methods have proven less effective. In one of the earlier studies conducted by the Mardor-Ram team, patients had a 73% response rate with average tumor shrinkage of 50%. Unfortunately, getting the CED process “just right is only one of several elements of this new potential treatment process required for a long-term successful outcome. The toxicity levels of the first drug trialed proved too high.
In a follow-up post we’ll examine these other elements necessary for success as well as discuss the future of CED.