At the last echo, we were talking, Julius had presented a case about a patient with brain mess from GYN malignancies, and the question was in terms of treatment for that and such. So, Julius, actually, you have homework for the next tumor board to give us a little update on that patient. Okay? And so, you know, we only had a few minutes, and so I knew this was going to be a whole other discussion. You know, it warranted a whole lecture, really, on it. So, just talking about brain metastases from GYN malignancies, let me see if this will hold on. Okay. There we go. So, brain mess from any gynecologic cancer is actually quite rare, except for trophoblastic disease, but from the solid tumors, those are pretty rare. So, the incidence rates, really, depending on the study that you look at, range with ovarian cancer, which has the highest incidence of brain mess of the GYN cancers, anywhere up to 2.2% uterine cancer, up to 1.2% and cervical cancer, really less than 1% of patients experience brain mess, but having a brain metastasis is significantly associated with worse prognosis. There's a 10% five-year survival rate and a median overall survival rate of five years. Patients are usually, so these aren't always recurrences. They're diagnosed synchronously with their primary tumor, so they're diagnosed with their uterine cancer, and they're actually found to have a brain mess in about 4% to 25% of patients. So, up to a quarter of patients have a brain mess at the time of initial diagnosis of their GYN cancer. And some of the presenting signs and symptoms are seizures, falls, headaches, or weakness. So, there has been a rise in the incidence of brain mess from ovarian and uterine cancers, and this has been attributed to the fact that we've got better treatment options for their primary cancers, their ovarian and uterine cancers and cervical cancers, so that increases a patient's lifespan, so that increases their likelihood that they may recur with a brain metastasis. The other reason why we think there's a rise in incidence is because we have better imaging modalities. Dr. Ueda was just talking about those different qualities of ultrasound versus CAT scan and finding the liver mess, but the same thing with brain metastases that now, with better imaging techniques, we're finding these brain metastases, perhaps, where we weren't 30 years ago, although they may have been present. There is a paucity of research, though. We really don't have a ton of research about outcomes and prognostic factors for GYN cancers because, again, these are really rare instances. We do know that a single metastasis and a good performance status at the time of diagnosis is a favorable prognostic factor, and, really, that's usually because they're usually eligible for surgical resection, and there can usually be a complete resection if there's only a single metastasis. Some poor prognostic factors are if this is a met from cervical cancer, if the patients have elevated CA-125, if it's a non-isolated brain met, so they have multiple brain mets, or if it's a symptomatic brain metastasis, and there's really no agreement on how we should be treating these. And we'll get into treatment shortly, but just in terms of the location, when somebody does have a brain metastasis, the cerebral area is the most common, but you can get them in the cerebellum or even in the leptomeninges. So just a quick overview that, in terms of in the cerebrum, 26% occur in the frontal lobe, 19% in the temporal lobe, 12% in the parietal lobe, and then, really, the other areas are much less. And these are just sort of how they can present. So for the frontal lobe tumor, they usually present with seizures. Temporal lobe, they may have auditory processing issues of the cerebellum. They may have an inability to coordinate voluntary movements in the brainstem, and it impairs the ability to walk, speak, swallow, they can have facial tension or vision changes, and the occipital lobe can lead to visual disturbances, loss of vision, or hallucinations. So how do we treat secondary brain tumors, so basically brain metastases? So whole brain radiation was the standard of care for over 50 years, but the issue with that is that it was associated with significant neurocognitive decline. And so surgical resection is an option, usually if it's an isolated brain matter, depending on the location within the brain. Radiosurgery or stereotactic radiosurgery has kind of surpassed whole brain radiation therapy because there's a lot of more brain-sparing techniques using stereotactic radiosurgery. And so in this one study, it showed that those who received stereotactic radiosurgery had better survival than those who received whole brain radiation therapy, but receiving any type of brain radiation, including radiosurgery, was not associated with survival benefit. So this is actually the time plot from that study, where if you see that stereotactic radiosurgery is this red line, and there really isn't a survival benefit based on whether somebody got no radiation or they got whole brain or they got stereotactic radiosurgery. Systemic therapy holds within its own challenges, and we'll get into what those are. And then, of course, there's palliative measures that can go along with these curative therapeutic measures, so corticosteroids, antiepileptics are an important part of the treatment regimen for patients with brain metastases. So the challenges of systemic therapy really arise because of the blood-brain barrier, the brain is a protected area, and it is purposely difficult for toxic agents to get into the brain. There's also a limited number of prospective trials on patients with brain metastases and GYN cancers. Most studies are underpowered, again, because of the rare instance of these. And most of the reports, at the end I'll show you some references, and I'll show you a chart that has a lot of the specific to GYN tumor brain metastases, a lot of the studies that were done, but most of them have less than 50 patients, and that includes a variety of tumors, so they included endometrial, ovarian, and cervical cancers. And a lot of patients with brain metastases have progressed on several prior chemotherapies or systemic therapies, so it makes it difficult in terms of subsequent regimens. So when would you consider systemic therapy, though, for brain metastases? I think this is one of the questions that Julius had asked last time. So in the upfront setting, meaning they are diagnosed with their primary tumor, so say with their ovarian cancer, and they're also found to have a brain met at the time of the diagnosis. So if they have multiple asymptomatic brain mets and a known effective therapy is available, you can consider systemic therapy. In the recurrent setting, really, we reserve systemic therapy after the failure of radiation and or surgery. So surgery or radiation are usually the mainstay for brain mets in a recurrent GYN cancer, and then only would you really move on to systemic therapy. So we do know that patients who receive single-agent therapies tended to fair poor compared to those treated with multimodal therapies, meaning the patients who only received, for example, chemotherapy or only received radiation did worse than those who had surgery and radiation or chemo and radiation. Again, small numbers of patients that we're looking at. So some of the things to consider when you're thinking about what type of treatment or treatments to offer are whether how many metastases patients have in the brain, where the location is. Is this something that is amenable to surgical resection? Is this something where if we did radiation, they'd have significant toxicity because of the location of it and if it's in the cerebellum, where they would potentially have ataxia afterwards, the size of the tumors, and then really important to consider the extent of their systemic disease, right? Is it they have only brain mets or do they have a lung full of nodules also? Do they have a belly that's a peritoneum that's riddled with tumor? So it really depends on, you really want to know what the extent of their systemic disease is before focusing on the brain mets. And then, of course, their performance status. Are we going to significantly worsen their quality of life by treating the brain metastases? So NCCN actually has guidelines specific for brain mets. And again, these are in resource-rich countries, right? And so usually MRI is used to evaluate the size, location, extent, and quality of the brain mets. And so if somebody presents and they have limited brain metastases on MRI and they have a known history of cancer, so say this is a recurrent disease. So somebody has a history of ovarian cancer five years ago and now they come in with brain mets on the MRI, well, then you can consider surgery for those brain metastases if they are limited. Really, you would resect it for management of their symptoms that are caused by the mass effect of these tumors or for treatment of patients with this newly diagnosed systemic disease. If you are not planning to resect the tumor, you mean you're not planning to undergo neurosurgery, then biopsy it if the concern exists. And again, I don't know what the ability for neurosurgery is at Uganda Cancer Institute or in the greater Uganda area, but this is, you know, surgery is something that we would consider. Now, if the patient has brain mets, but they don't have a history of cancer, well, you've got to work up why they have these brain metastases. And so, you know, a full workup in terms of whether it's a CT scan or a PET-CT scan, depending on the likely areas of where the tumor may have originated. And again, and then they would recommend either biopsy or resecting the tumor that's found outside of the central nervous system to confirm the cancer diagnosis, to establish the primary tumor. If in this workup you do not find another tumor that's readily accessible for biopsy, then only would they recommend going in for surgery for a CNS met, for brain metastasis without knowing where, what the primary tumor is. Now, if somebody has disseminated systemic disease, so you're diagnosed with somebody with stage four ovarian cancer, and they have a really poor performance status, but they have a brain met that's affecting their quality of life, well, then you can consider whole brain radiation therapy, stereotactic radiosurgery, or consider just palliation. And then finally, if they're newly diagnosed or they have stable systemic disease, so they have ovarian cancer, but it's amenable to surgery, or they don't really have progression of disease there, and you have reasonable systemic treatment options, so you've diagnosed somebody with a primary ovarian cancer, it's their first diagnosis. You know that these are usually chemosensitive, well, then those patients, we would prefer doing stereotactic radiosurgery for their brain metastases, but in addition, treating their initial, treating their primary tumor. And then just in terms of follow-up, usually these patients will get a brain MRI every few months for a couple of years, and then we space those out to every four to six months, and that's indefinitely. And then again, if there was recurrence, depending on where it is and whether it's isolated to the brain or if they have other systemic disease, again, would determine whether surgery versus radiosurgery versus whole brain radiation therapy or systemic therapy would be appropriate. So this was just that article that I was talking about, one of the references that actually I had a really nice table summarizing all the main findings in the largest GYN metastases brain met series. So I just wanted to point out to you just, you know, the histologies of these, again, most of these combined tumor sites, so this one had ovary, uterine, corpus, this one was endometrial, this one, I believe, was just endometrial, this one combined several different tumor sites, this one was just an endometrial study. And again, if you look at the numbers of patients that were included, you know, 42, 47, one of the higher, then this one was 174, this was all in ovarian cancer patients. But again, there, if you look at their time to brain mass was about 26 months, and so this is, and the age was, the average age was 60. But this was a really nice table kind of summarizing the information that is actually out there for GYN brain mass. Again, this study had 100 patients, but again, it was spread out between endometrial, ovarian, and cervical cancers. And so that was, so I just wanted to do a quick overview of brain mass and GYN cancers. It was quick also because we just don't have that much information available. So these were the references that I used. You have those, and Susan can certainly send out this presentation just so you have the information. But Julius, I think you're, everybody's still on. For the next echo, if you could just give us an update on your, the patient that we discussed last month, that would be really helpful.

brain metastases

gynecologic malignancies

incidence rates

prognosis

treatment options