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

Anthony P Y Liu; Gang Wu; Brent A Orr; Tong Lin; Jason M Ashford; Johnnie K Bass; Daniel C Bowers; Tim Hassall; Paul G Fisher; Daniel J Indelicato; Paul Klimo; Frederick Boop; Heather Conklin; Arzu Onar-Thomas; Thomas E Merchant; David W Ellison; Amar Gajjar; Giles W Robinson

doi:10.1093/noajnl/vdaa168

journal article Open Access Dec 15, 2020

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

Anthony P Y Liu

Gang Wu

Brent A Orr Tong Lin

Jason M Ashford Johnnie K Bass Daniel C Bowers Tim Hassall Paul G Fisher Daniel J Indelicato Paul Klimo Frederick Boop Heather Conklin Arzu Onar-Thomas Thomas E Merchant David W Ellison Amar Gajjar

Giles W Robinson

Neuro-Oncology Advances Vol. 3 No. 1 · Oxford University Press (OUP)

View at Publisher Save 10.1093/noajnl/vdaa168

Abstract

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 &lt;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.

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Details

Published: Dec 15, 2020
Vol/Issue: 3(1)
License: View

Authors

A

Anthony P Y Liu

Department of Oncology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA

G

Gang Wu

Department of Pathology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA

B

Brent A Orr

Department of Pathology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA

T

Tong Lin

Department of Biostatistics, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA

J

Jason M Ashford

Department of Psychology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA

J

Johnnie K Bass

Department of Rehabilitation Services, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA

D

Daniel C Bowers

Division of Pediatric Hematology and Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, USA

T

Tim Hassall

Queensland Children’s Hospital, Brisbane, Queensland, Australia

P

Paul G Fisher

Department of Neurology, Stanford University, Palo Alto, California, USA

D

Daniel J Indelicato

Department of Radiation Oncology, University of Florida College of Medicine–Jacksonville, Semmes Murphey Clinic, Memphis, Tennessee, USA

P

Paul Klimo

Department of Surgery, St. Jude Children’s Research Hospital, Semmes Murphey Clinic, Memphis, Tennessee, USA; Department of Neurosurgery, University of Tennessee Health Science Center, Semmes Murphey Clinic, Memphis, Tennessee, USA; Le Bonheur Neuroscience Institute, Le Bonheur Children’s Hospital, Semmes Murphey Clinic, Memphis, Tennessee, USA; Semmes Murphey Clinic, Memphis, Tennessee, USA

F

Frederick Boop

Department of Surgery, St. Jude Children’s Research Hospital, Semmes Murphey Clinic, Memphis, Tennessee, USA; Department of Neurosurgery, University of Tennessee Health Science Center, Semmes Murphey Clinic, Memphis, Tennessee, USA; Le Bonheur Neuroscience Institute, Le Bonheur Children’s Hospital, Semmes Murphey Clinic, Memphis, Tennessee, USA; Semmes Murphey Clinic, Memphis, Tennessee, USA

H

Heather Conklin

Department of Psychology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA

A

Arzu Onar-Thomas

Department of Biostatistics, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA

T

Thomas E Merchant

Department of Radiation Oncology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA

D

David W Ellison

Department of Pathology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA

A

Amar Gajjar

Department of Oncology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA

G

Giles W Robinson

Department of Oncology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA

Funding

American Lebanese Syrian Associated Charities

National Cancer Institute Cancer Center Award: P30CA021765

Cite This Article

Anthony P Y Liu, Gang Wu, Brent A Orr, et al. (2020). Outcome and molecular analysis of young children with choroid plexus carcinoma treated with non-myeloablative therapy: results from the SJYC07 trial. Neuro-Oncology Advances, 3(1). https://doi.org/10.1093/noajnl/vdaa168

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

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