How would you treat a patient with HER2 positive CNS only progression on fam-trastuzumab which had previously progressed on tucatinib/capecitabine/trastuzumab, and has failed both SRS and WBRT?

I would present or refer her case to a multidisciplinary tumor board to 1) review her MRI to confirm there is progression vs. therapy changes, 2) see if she is a candidate for resection or irradiation of the progressing lesion (possibly using bevacizumab to reduce risk of radiation necrosis), and 3) review her systemic treatment and clinical trial options.

If she can get local therapy to the CNS lesion and has no progression elsewhere, I would continue fam trastuzumab. If local therapy can't be u...

What's the definition of 'CNS progression', and does it truly preclude additional RT?

If numerous (> 3, >10, > whatever cut-off people use) intraparenchymal metastases without LMD, should consider repeat SRS, regardless of number of lesions. Here is a case report of 37 lesions treated: Hyde et al., PMID 29503779.

Anecdotally, people have treated > 50 lesions in a single radiosurgery setting. Not the routine answer, but when there are no other good options (h/o WBRT, progressing on multiple lines o...