Abstract
BACKGROUND
LMC is a rare complication of systemic cancer metastasis to the leptomeninges. Although first described in 1870 treatment options remain few for this rapidly fatal condition commonly excluded from clinical trials and disease site guideline updates. Whole brain radiation therapy (WBRT) and intrathecal (IT) chemotherapy are commonly employed and there is growing evidence for systemic therapies that cross the blood brain barrier. Disseminated necrotizing leukoencephalopathy (DNL) is a self-limited rare treatment-related radiographic finding variably associated with clinical decline and often misdiagnosed as progression or infection. DNL has been reported in patients exposed to IT chemotherapy and CNS irradiation. Our lab recently published improved LMC control with extended survival after standardization of Ommaya clinic IT treatment regimens, although with increased incidence of DNL.
METHODS
We retrospectively analyzed patients with LMC treated with IT chemotherapy after WBRT between 2017 – 2020. We reviewed sequential brain imaging over the treatment course to determine if there were predictive CSF markers associated with the development of DNL.
RESULTS
Of the 41 patients evaluated, 24% (n=10) developed DNL at a median 24-weeks after start of IT chemotherapy and WBRT. Of the patients with radiographically assessed DNL, 80% (n=8) experienced elevated CSF protein and 40% (n=4) had elevated white blood cells within 8-weeks prior to radiographic determination of DNL. Cytology remained benign and glucose was not significantly changed prior to DNL development.
CONCLUSION
Given the poor outcome of LMC, there is a need for treatment standardization and better understanding of treatment-associated radiographic changes. Evaluation of CSF markers to predict impending development of DNL in this treatment population might limit radiographic misdiagnoses and patient clinical decline as well as offer a potential window of opportunity for treatment de-escalation.