In oligometastatic NSCLC with a solitary brain metastasis and lung primary amenable to SBRT, how would you sequence first-line systemic therapy versus local therapy to the lung after treatment of the CNS metastasis?

Would generally favor appropriate first-line systemic therapy whether that be immunotherapy +/- chemo vs. targeted therapy and if at least stable disease at the next surveillance imaging (~3 months), go ahead and consolidate with SBRT. I don't think it would be wrong to do SBRT upfront here but the added benefits of:

1. Having some untreated diseases to monitor the response.
2. Gives you a window to make sure they don't blossom further metastatic disease on systemic therapy
3. May get less pushback on approval for SBRT after an interval of stability on systemic therapy. 

You can do it either way. 

SINDAS trial (Ph. 3) gave upfront SBRT followed by TKI in EGFR mutation+ patients. 

Other trials (MDACC Ph. 2, UTSW Ph. 2, NRG Onc Ph. 3 - although negative) gave upfront SOC systemic therapy and if the disease remained stable, proceed with SBRT.

How big is the brain metastasis? If it's already large and won't be resected, I'd start with SBRT followed by systemic therapy and then lung SBRT if necessary. On the other hand, if the brain metastasis was small, I'd start with systemic treatment and repeat an MRI of the brain in a couple of months to assess response vs. growth, and after the chemotherapy was completed, would Rx both the brain and lung, likely sequentially.

I would treat both upfront at the same time -- 54 Gy/18 Gy to lung and 27 Gy/9 Gy to brain on a M/W/F.

Could do it either way.