Diagnosis of leptomeningeal metastasis through identification of circulating tumor cells in cerebrospinal fluid using the TargetSelector™ assay

Wooster, Margaux; McGuinness, Julia E.; Fenn, Kathleen; Singh, Veena; Franks, Lauren; Lee, Joe; Cieremans, David; Lassman, Andrew B.; Hershman, Dawn L.; Crew, Katherine D.; Accordino, Melissa K.; Trivedi, Meghna S.; Iwamoto, Fábio M.; Welch, Mary; Haggiagi, Aya; Schultz, Robbie D.; Huynh, Lan; Sales, Edgar; Fisher, Deanna; Mayer, Julie Ann; Kreisl, Teri; Kalinsky, Kevin

doi:10.21203/rs.3.rs-206232/v1

Cited by 2 publications

(1 citation statement)

References 27 publications

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“…Higher volumes can increase diagnostic yield, but this was limited in the current patient due to a Chiari malformation. Using tests for CSF circulating tumor cells is also felt to increase the sensitivity of lumbar puncture [ 10 ], but our lab does not regularly perform these in-house, and at the time, commercial testing was not available. Additionally, it is not clear that sarcoma cells would be well captured by current commercial testing.…”

Section: Discussionmentioning

confidence: 99%

Isolated Leptomeningeal Progression in a Patient with NTRK Fusion+ Uterine Sarcoma: A Case Report

et al. 2021

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While neurotrophic tropomyosin receptor kinase (NTRK) fusions represent rare oncogenic drivers (<1% of solid cancers), the recent approval of NTRK inhibitors (larotrectinib and entrectinib) led to dramatic responses in patients with NTRK fusion+ tumors. Both drugs have phase I data, demonstrating efficacy in the central nervous system (CNS), including both primary brain tumors and brain metastases. We present a 29-year-old woman who was diagnosed with <i>NTRK3-SPECC1L</i> fusion+ undifferentiated uterine sarcoma and underwent resection, chemotherapy, and radiotherapy. Two years later, lung metastases were discovered. She was started on larotrectinib with complete response. She remained stable on larotrectinib until she presented with altered mental status and seizures. MRI demonstrated leptomeningeal enhancement, but because leptomeningeal progression from sarcoma is exceedingly rare and her symptoms improved dramatically with antiepileptics, these findings were initially attributed to seizures. After 2 unrevealing lumbar punctures and stable systemic imaging, a brain biopsy demonstrated metastatic sarcoma, still showing NTRK positivity. She underwent whole brain radiotherapy and was switched to entrectinib, but had clinical progression 1 month later and transitioned to hospice. This case demonstrates the efficacy of NTRK inhibitors in rare and aggressive cancer but highlights that these patients can develop isolated CNS progression even in the setting of CNS-penetrant drugs. CNS progression can occur if there is incomplete CNS drug penetration, discordance in molecular profiles between CNS and systemic disease, or acquired NTRK inhibitor resistance. In this case, CNS disease maintained the NTRK fusion status, but either inadequate CNS penetration or development of a resistance gene may explain the isolated CNS progression.

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Section: Discussionmentioning

confidence: 99%