Joyce O’Shaughnessy, MD: So, walk us through, what did you think about this patient here? You found the brain met because she had headaches. That's how you found her brain met and then was just one, so you treated it. So, what was your thinking about what to go on to next?

Virginia Kaklamani, MD: So, my thinking after that was to give TDXD to the patient. She was able to be on TDXD for quite some time before her cancer progressed. And at that point, I think, again, my third-line favorite regimen would be HER2CLIMB given the, again, level one evidence in that setting.

Joyce O’Shaughnessy, MD: And how often should we be doing brain MRIs once a patient like this has developed a brain met?

Andrew Brenner, MD: Well, there's two different components to that. One of them is the patient who is clinically asymptomatic after treatment and the guidelines recommend every two to three months. And that's what I do in my practice. I actually do every two months. I go on the shorter side because it gives me a little bit more time to be proactive. Sometimes you can monitor lesions to see what's going on and get a little bit more clinical data. So, the guidelines say every two to three months once you've established that they have brain metastasis and then you can expand that time interval if they continue to have stable disease thereafter. And then there's the patient who has any sort of symptom. And so, the guidelines support that at any time that you have a clinical index of suspicion that there's something new going on, you can get the MRI. And so, if a patient has any change in neurologic symptoms, I will go ahead and get an earlier MRI.

Joyce O’Shaughnessy, MD: And so, this patient, she's getting TDXD let's say and you're getting brain MRIs every couple three months there Heather. And now she's got another couple have come up. But systemically she's still stable on the TDXD. How do you think about that?

Heather McArthur, MD: Well typically, and this is where multidisciplinary collaboration is so critically important, it depends on what's possible locally in terms of additional SRS or less frequently whole brain radiation or neurosurgery, whether those are appropriate modalities in that case if they are. Then I would continue on the systemic therapy assuming the non-CNS disease is controlled, and local strategies are important for controlling the active brain metastasis.

Joyce O’Shaughnessy, MD: And is that what you would do to and reduce to more SRS assuming it was feasible?

Andrew Brenner, MD: Yes, that's what the data currently shows that for patients who have endocranial progression with that extra cranial progression that you do local therapy first and you say you continue with the systemic agent and maximize your use of that. You know and there's the question of if the patient has new has lesions that are recurrent in an area that has already been treated then it becomes a little bit more complicated. And then in that setting you need to consider what your salvage regimens are if the patient is a candidate for whole brain with hippocampal avoidance for example if they've already received SRS. There's also this concept that we have which we haven't really got into which is brain metastasis velocity. And so, one thing we need to decide in terms of local therapy is do you do SRS for a patient if they have one or two brain metastases? What was the timeline since their prior brain metastasis? So, some of the studies that look at salvage therapy suggest that if a patient has a rate of greater than four brain metastasis per year and obviously that denominator can be within a six-month period, etcetera, two within six months, then you probably need to move from a stereotactic patient approach to a whole brain type of treatment or at least consider whole brain with hippocampal avoidance for those patients with a higher brain metastasis velocity.

Joyce O’Shaughnessy, MD: Just to play a little devil's advocate I think a lot of the ASCO and NCCN guidelines about just using local therapy for the brain and stay the course on your successful systemic therapy came before we had some of the newer treatment options where we can get, because if somebody just keeps popping up with these things or maybe there's multiple or maybe they're big or what have you, isn't it time to think about something that does a little better job for the brain because they're clearly in the brain progressing on what they're on.

Andrew Brenner, MD: So, something to keep in mind how HER2CLIMB was conducted and how I actually conduct my practice is those patients if they had active brain metastasis that they had to be clinically relatively stable and that they could have time for systemic therapy to work. Patients with very large tumors causing a lot of mass effect or patients who have disease in a very eloquent area, if they have something in the, you know, near the motor cortex and there's some peritumoral edema there and you can get control of that with steroids but you might not have time to wait for a systemic regimen. So, you also need to consider as was done in the study whether the how symptomatic the patient is from the brain metastasis in terms of choosing an active CNS regimen systemically versus local therapy.