Andrew Brenner, MD: This is a 62-year-old high school guidance counselor who was diagnosed with stage two. She was ERPR negative, HER2 positive. In the new age of in setting, she received pertuzumab, trastuzumab, plus chemotherapy, and then she went on in the post-surgical setting with residual disease, received TDM-1 as per CATHERINE. Five years after the completion of her adjuvant therapy, she presented with pulmonary metastases. She was treated with pertuzumab, trastuzumab, and docetaxel for six cycles. And then she went on to maintenance of pertuzumab and trastuzumab for three years. At routine clinic visits, she started complaining of headaches. And the MRI showed a single 1.5cm brain metastasis. Her pulmonary mets were stable. She received SRS for the brain metastasis followed by continuation of pertuzumab and trastuzumab. And then 10 months later, she complained again of headache and mild vertigo. And now she has two new lesions, each about one centimeter. Her pulmonary mets still are stable. So, the question is how we would treat this patient who has, again, a second brain metastasis. This time she has two new brain metastasis, one centimeter each, but her extracranial disease is well controlled.

Joyce O’Shaughnessy, MD: Well, we spoke about this. We kind of foreshadowed this patient. I think we were all kind of thinking that maybe every dog gets one bite. We might go with another round of SRS provided it was feasible. Let me ask you this. Does the size make a difference here? You know, if she had a 4.5cm lesion, is there a certain limit that we have to be aware of for SRS?

Andrew Brenner, MD: Generally speaking, we limit it to three centimeters or less. Once you get above that, you're starting to move away from what is considered radiosurgery, and it's really just more like IMRT, and it needs fractionation. And so really, there is a size limitation. On top of that, the larger the lesion, the more symptomatic they are likely to be. A significant question is for lesions that are larger in size and low in number, potentially craniotomy, because you can very quickly render that patient free of symptoms, provide some room, and then you can follow up to the tumor bed later after you've debulked that tumor with SRS. In the brain metastasis world, there's a little bit more discussion now about the sequence in these patients who are getting craniotomy of stereotactic radiosurgery. Unfortunately, about 10% of patients who have a craniotomy for a brain metastasis will develop leptomeningeal disease. And some studies seem to show that if you do SRS before the surgery, you can reduce the chances of developing leptomeningeal disease, which when it occurs, is obviously devastating.

Joyce O’Shaughnessy, MD: Is that just the posterior fossa, or is that anywhere? Should we be considering SRS first, just one course, then craniotomy? If it's a frontal lesion, parietal, or is it really? Is it the posterior fossa where the leptomeningeal risk is?

Andrew Brenner, MD: I think it's really anywhere. But the real question is, is it surgically resectable? And certain parts of the brain obviously are not as resectable as others. And you have more frontal lobe than you do other lobes. It's a larger part of the brain, and we tend to see more in the frontal lobe in terms of supratentorial disease. Luckily, that tends to be more amenable to surgery, especially if it's in a non-dominant hemisphere. So, it really can be anywhere that you could take that approach, but it really just is whether or not you're dealing with a surgically resectable lesion, which is not going to harm the patient by doing surgery.

Joyce O’Shaughnessy, MD: A lot of times we don't have the luxury, because it takes just a little bit to get the insurance approval and get the neurosurgeon, the rad onc, lined up for the SRS. And a lot of times these patients are in the hospital on high dose steroids. They have the big metastasis. I don't know if you have any approaches to that.

Andrew Brenner, MD: It does take a very cohesive team to deal with this, and luckily, I think in the inpatient setting we've got a very dedicated group of neurosurgeons who consult us very early on before taking the patient to surgery. That's the first step, is when they show up, the first thing that usually happens is neurosurgery gets consulted, and then they might end up going straight to craniotomy. So, it involves having a neurosurgery team that is very in tune to multidisciplinary discussion at the time of the diagnosis of the brain metastasis, and then working very closely with the radiation oncology team, and then kind of having the medical oncologist and neuro-oncologist kind of help to cement the process.

Joyce O’Shaughnessy, MD: This happened to one of my young patients, unfortunately. We were able to get the symptoms and swelling down pretty fast. She was actually in the ICU, but the steroids. The steroids did a great job. Let's just take a little break here and get her discharged, get the SRS, and then do the surgery.

Andrew Brenner, MD: So, the nice thing about steroids is they give you a very quick answer. If you give a nice high dose right up front, you're going to see symptomatic improvement in 24 to 48 hours. So, it gives you a very quick window in terms of how this patient is going to do. A patient who you give steroids at the time they present to the emergency room and within a day or two they're less symptomatic, you know you have time to make appropriate arrangements to treat that patient's brain metastasis.