Outcome and molecular analysis of young children with choroid plexus carcinoma treated with non-myeloablative therapy: results from the SJYC07 trial

Abstract

BACKGROUND: Choroid plexus carcinoma (CPC) is a rare and aggressive tumor of infancy without a clear treatment strategy. This study describes the outcomes of children with CPC treated on the multi-institutional phase 2 SJYC07 trial and reports on the significance of clinical and molecular characteristics. METHODS: Eligible children <3 years-old with CPC were postoperatively stratified to intermediate-risk (IR) stratum if disease was localized or high-risk (HR) stratum, if metastatic. All received high-dose methotrexate-containing induction chemotherapy. IR-stratum patients received focal irradiation as consolidation whereas HR-stratum patients received additional chemotherapy. Consolidation was followed by oral antiangiogenic maintenance regimen. Survival rates and potential prognostic factors were analyzed. RESULTS: Thirteen patients (median age: 1.41 years, range: 0.21-2.93) were enrolled; 5 IR, 8 HR. Gross-total resection or near-total resection was achieved in ten patients and subtotal resection in 3. Seven patients had TP53-mutant tumors, including 4 who were germline carriers. Five patients experienced progression and died of disease; 8 (including 5 HR) are alive without progression. The 5-year progression-free survival (PFS) and overall survival rates were 61.5 ± 13.5% and 68.4 ± 13.1%. Patients with TP53-wild-type tumors had a 5-year PFS of 100% as compared to 28.6 ± 17.1% for TP53-mutant tumors (P = .012). Extent of resection, metastatic status, and use of radiation therapy were not significantly associated with survival. CONCLUSIONS: Non-myeloablative high-dose methotrexate-containing therapy with maximal surgical resection resulted in long-term PFS in more than half of patients with CPC. TP53-mutational status was the only significant prognostic variable and should form the basis of risk-stratification in future trials.2632-2498Liu, Anthony P Y <br />Orcid: 0000-0002-8597-9128 <br />Wu, Gang <br />Orcid: 0000-0002-1678-5864 <br />Orr, Brent A <br />Lin, Tong <br />Ashford, Jason M <br />Bass, Johnnie K <br />Bowers, Daniel C <br />Hassall, Tim <br />Fisher, Paul G <br />Indelicato, Daniel J <br />Klimo, Paul Jr <br />Boop, Frederick <br />Conklin, Heather <br />Onar-Thomas, Arzu <br />Merchant, Thomas E <br />Ellison, David W <br />Gajjar, Amar <br />Robinson, Giles W <br />Orcid: 0000-0001-7441-9486 <br />Journal Article <br />Neurooncol Adv. 2020 Dec 15;3(1):vdaa168. doi: 10.1093/noajnl/vdaa168. eCollection 2021 Jan-Dec. <br />