How do you approach treatment for patients with ALK+ mNSCLC who have multifocal or leptomeningeal CNS progression while on first-line targeted therapy?

Leptomeningeal disease is one of the more challenging scenarios to manage in a patient with ALK rearranged lung cancer. One must work carefully with the radiation oncologist and factor in imaging findings as well as patient symptomatology to make the best decision moving forward. Radiation options i...

It is reasonable to use peripheral ctDNA testing to look for ALK resistance mutations which might suggest a 3rd generation inhibitor like lorlatinib is the next best therapeutic step. It is important to note, however, that in the absence of systemic progression, ctDNA testing may have limited sensit...

While I find brigatinib to be much better tolerated and highly active post-alectinib, leptomeningeal disease can lead to rapid deterioration and my preference is to begin lorlatinib which has the highest CNS efficacy. Craniospinal irradiation, potentially with proton therapy, is something we have co...

LMD usually becomes symptomatic soon so palliative WBRT would be indicated. Should also image the spine to see if any visible disease can be controlled with localized radiation. I have very rarely done CSI for these cases as it is very toxic as was mentioned previously, but depends on patient perfor...

If 2nd line systemic therapy won't work, then there's unfortunately little hope for anything good to come out of WBRT.