So, our next speaker is Dr. Kanzioka, who will be speaking and accepting an award on behalf of Dr. Amparo-Wolf. The award is the WNS-CNS Joint Section on Tumors Neuro-Oncology Trainee Award. Thank you very much. It's a real pleasure to accept this award on behalf of a tremendous resident from the University of Western Ontario, who spent a year with me in New York, and is going to do a neuro-oncology fellowship at MD Anderson. I want to hire this person if she would be willing to live and move to New York City. That's how good she is, so my advice is find her and give her a job. So this is a topic near and dear to many hearts. This is hopefully the largest study ever done on this topic. It may never be repeated, although I hope it will be repeated. Obviously, we know what radiosurgery is. The fear about radiation-induced malignancy is not from the lesion itself. In fact, the dose is so high to the tumor that it's destructive of cells. That's not really a concern for mutagenesis. It's really the low dose, which doesn't destroy tissue but can modify tissue. And of course, we're using this for virtually every structural disorder that exists in the brain. So for vestibular schwannomas, where the cochlea might be getting too gray, is this a risk as opposed to the tumor itself for delayed malignancy in the bone in the brain beside it and the subcutaneous tissues? Meningiomas, tumors of bone, brain, or scalp, pituitary tumors, the infertemporal region, the brain itself, the skull base. Trigeminal neuralgia, the target is extremely small, but it's a higher dose, so the volume of tissue getting that lower dose is still important. And arteriovenous malformations, this really represents the common benign entities that radiosurgery is used for. So this remains a concern of patients and clinicians, and we talk about this virtually every day in our office. Is it a myth that radiation can cause cancer, or is it a concern? And of course, in the background of this, we know that external beam radiotherapy, which has been used for a long, long time, particularly in the old days of bitemporal fields, had huge volumes of tissue being radiated at these lower doses. And the risk was always about 1 in 100 or 1 in 200 patients would get a secondary tumor of some kind. It could be a pituitary adenoma followed by a meningioma, or it could be a malignant tumor. And that's a concerning number. And of course, there are case reports of secondary malignancies that meet the Cajon's criteria, which means that the secondary tumor had to be in the field, there had to be a time delay, and you had to know the pathology. The pathology couldn't initially have been cancer. So the objective of this study was to quantify the risk of secondary malignancy and malignant transformation, and to compare this to something, and the comparison was to the Central Brain Tumor Registry of the United States. So we looked at five centers from 1987 to 2016 for these large volume benign entities, and looked at both malignant transformation at the target site or anywhere in the brain, we'll call that delayed radiation-associated tumors, with a minimum of two-year follow-up. So you can see the numbers, about 9,000 patients in total, vestibular schwannomas at 1,600, 2,600 meningiomas, hemangioblastomas were in this group as well, some other schwannomas, pituitary tumors, and 2,000 AVMs. Some had prior resections. All of these were non-previously irradiated, except for a couple of examples that I'll show you. Median follow-up was five years, and importantly, 1,200 patients with more than 10 years, and 430 patients with more than 15 years of follow-up. And I quote patients that the risk is less than 1 in 5,000 over the next five to 30 years. That's kind of a statement that I use. So how well does that hold up? Well, what we found was two cases of malignant transformation of vestibular schwannomas at 8 1⁄2 and 11 1⁄2 years that were pathologically verified. It was one case of a presumed grade 1 meningioma, there was no tissue before that, that became grade 3 meningioma at 3.6 years. Did it become this, or was it already that? That's one of the issues with no prior histology. And looking at that incidence, it's about 8 per 100,000 patient years for benign tumors. If you look at any radio-associated new malignancy, there were three new malignant brain tumors reported. One vestibular schwannoma patient, a distant intracranial malignancy at 4 years, meningioma at 9 years, and a pituitary adenoma with an RSTL sarcoma locally at 13 years. So the incidence of a new malignancy after radiosurgery, either locally or distant, was 5 per 100,000 patient years. And the details of these cases are, as shown, the radiation dose is relatively low and standard. Transformation to malignant peripheral nerve sheath tumors, malignant schwannoma, meningioma, distant osteosarcoma, as you can see here. So the actual 10-year risk of developing malignancy after radiosurgery is 0.001%. That's another way to tell a patient about this risk. And if you look at the Central Brain Tumor Registry of the United States, the risk of a primary malignant or non-malignant brain and other CNS tumors is about 22 per 100,000, and 7.15 per 100,000 for malignant tumors, which is our concern, not the benign tumors. So, in conclusion, this is the largest study to date on this question. Physicians can safely counsel patients that the risk of malignancy after radiosurgery remains extremely low, even at follow-up more than 10 years. And between 5 and 8 per 100,000, depending on how you look at it, the risks are comparable to the Central Brain Tumor Registry at 7 per 100,000. So there appears to be no material increased risk in a large population base after radiosurgery. Of course, any patient can have anything that can happen, but looking at it from population health, the risk remains very, very low. Thank you.

Dr. Kanzioka

Dr. Amparo-Wolf

WNS-CNS Joint Section on Tumors Neuro-Oncology Trainee Award

radiation-induced malignancy

radiosurgery