The management of brain meds in the area of targeted therapies, immunotherapy. Uh So as we all know, cns metastases are very common in non small cell lung cancer patients, about 10% of patients actually present with CNS involvement. Another 20 to 40% will develop over time. Um The rates are even higher in those patients that have um that have uh driver oncogenes, especially EGFR and ALK mutations where it's up to 60%. So, uh this is certainly very important um in terms of someone who has a single brain metastasis, uh the the flow sheet that she has written out here, basically, if you need pathology, if they're symptomatic on steroids or if primary radiation is not technically feasible or safe, then surgery and radiation is gonna be most appropriate. Um That would be especially if it's in an eloquent area, brain stem for those that are asymptomatic um with and without steroids and there's no other indication or need for surgery or pathology than proceeding with stereotactic radiosurgery. Uh, surgery does not improve control of our SRS alone. Um Certainly with the radiation. Um there's so this was a trill of study, sorry, this was a secondary analysis of SRS versus surgery. It was basically an EO RT C study, looking at the role of a whole brain radiation after local therapy. Um, peop the patients either got surgery or stereotactic brain radiation. They ended up having 260. Some patients with 1 to 3 brain meds all four centimeters or smaller in size, a little bit more. Um, of percent of the patients underwent SRS as compared to surgery. Those that had surgery, tended to have larger tumors. They more commonly had a single metastasis and there was variations in terms of the location. Um The risk of local recurrence was similar um between surgery and stereotactic radiation, but it varied according to time. Um So those patients that um oh sorry. So the time of recurrence um essentially for those patients that um had surgery as compared to SRS, it was more frequent that they had an earlier recurrence. Uh getting stereotactic radiation was associated with a later recurrence. Um for ogo metastatic breast cancer. Um Certainly, if they're symptomatic on steroids, again, require pathology or can't do the radiation, then you could do consider surgery to the problematic lesion with radiation to follow um or, and, or radiation to the other lesions as well. Uh Stereotactic alone could be considered to those that again, have generally smaller lesions in less eloquent areas are not causing increased intracranial pressure. For those that have extensive brain metastases. Generally, you're deciding between whole brain radiation and hospice. This is also evolving. There are studies that are looking at up to 15 brain metastases being treated with stereotactic radiation. So I think this uh trail will end up getting a little bit different over time. Um So there's multiple systemic therapies, some of them have very good or reasonable penetration into the CNS. Um but there's definitely variety amongst them and so common molecular targets. Um and treatments are listed here. Um We touched on some of these and other talks. Uh The molecular mutations of brain meds may be discordant with those of the primary tumor. I think that's pretty interesting thought. So, um brain metastases in the setting of first generation TKIS are less likely to have acquired um resistance than sites of extracranial disease progression. Um So NCCN guidelines, essentially a trial of systemic therapy uh with good CNS. PA NR can be considered with those patients that have small asymptomatic brain metastases. There's no data in perspective, clinical trials comparing the strategies and you need to consider what it would mean and what the impact would be on patients if you delay um radiation and um more definitive local therapy. So management of brain metastases and TK I naive EGFR, non small cell lung cancer. So um essentially this was um a comparison where patients were getting stereo ttic radiation followed by TK I group two, got whole brain followed by TK I or group three just got uh TK I with radiation reserved for when there was progressive disease. Uh There was definitely an improvement in terms of overall survival. Those that received the stereotactic radiation with TK I fared the best they did the best. Um So this show that deferral of radiation was associated with worse overall sur uh survival outcomes even in the whole brain group where patients had an unfavorable diagnosis or prognosis rather. So this is a meta analysis of upfront radiation versus uh TKIS alone or Latin Burger Finin I for the most part. Um So 13 studies, essentially, what this shows us is that they um with the um the overall survival was better in those patients that um we're getting the upfront radiation uh in most cases. But at the same time, um there's information within the, the study itself that um of course says additional studies are going to be necessary to bear this out further. Uh this study. Um So, egfr mutations um flora trial showed superiority over git nib or Latin I. Um but earlier drugs do have activity. You do want to proceed with caution. Um And you don't wanna use radiation in conjunction or whole brain radiation in conjunction with these uh overall survival is worse with concomitant drugs and there's also higher toxicity associated with it. So, um many groups favor stereotactic radiation followed by uh Inchin or Riot tib or satin. Um Systemic therapy alone can be considered. So again, she has different um patients and directed therapies uh routinely, you want to hold the TK I until completion of treatment and then you could resume usually a day or two after stereotactic radiation. Um Again, you do want to use caution because of increased rates of toxicity with concomitant treatment. Um for those that uh cancers that don't have driver mutations, small asymptomatic or minimally symptomatic um treatments that uh disease that has resolved with the use of steroids. Um You can consider immunotherapy or other directed treatment plus or minus stereotactic radiation um for those lesions that are larger um or again, that um are minimally symptomatic that resolve with steroids again. Um Stereotactic radiation is often considered more upfront in those settings with additional treatments to follow. So upfront, uh immunotherapy with SRS leads to lower brain met velocity uh overall. So the Bible was improved with stereo tactic radiation and immunotherapy versus stereo tactic alone in this study. Uh The velocity um with development of new meds per year was uh significantly improved with the addition of upfront stereotactic radiation. There was no significant difference in terms of neuro death. Um This may help with avoiding whole brain radiation and associated toxicities and long term sequela. So, considerations, there's um new data and this was presented last week at Astro which suggests that some of the concerns that we have about long term sequela associated with radiation actually may be reversible. Um 40% have a complete recovery 75% of partial recovery. Uh Certainly stereotactic radiation alone, those patients are more likely to recover than those with whole brain. Uh There's no difference in terms of um overall rate of improvement though between stereo and whole brain again, multidisciplinary approach, consultation with radiation oncology is strongly recommended. And um certainly, you know, we want to think about if you delay therapy for these people, what would be the um result of that? And could there be uh subsequent neurocognitive um or neurologic deficits with delay of radiation? Uh There's no randomized evidence to guide upfront versus delayed radiation. Uh long term cns control is extremely important um for these patients. And so we know whole brain works, but there's cognitive side effects associated with that stereo works less cognitive side effects. Um But we know that the disease itself, if it progresses is going to cause problems and so progressive disease 100% of the time. Um if given the opportunity will end up causing uh cognitive changes and systemic therapy may as well. So, thank you.
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