TY - JOUR
T1 - Molecular grouping and outcomes of young children with newly diagnosed ependymoma treated on the multi-institutional SJYC07 trial
AU - Upadhyaya, Santhosh A.
AU - Robinson, Giles W.
AU - Onar-Thomas, Arzu
AU - Orr, Brent A.
AU - Billups, Catherine A.
AU - Bowers, Daniel C.
AU - Bendel, Anne E.
AU - Hassall, Tim
AU - Crawford, John R.
AU - Partap, Sonia
AU - Fisher, Paul G.
AU - Tatevossian, Ruth G.
AU - Seah, Tiffany
AU - Qaddoumi, Ibrahim A.
AU - Vinitsky, Anna
AU - Armstrong, Gregory T.
AU - Sabin, Noah D.
AU - Tinkle, Christopher L.
AU - Klimo, Paul
AU - Indelicato, Danny J.
AU - Boop, Frederick A.
AU - Merchant, Thomas E.
AU - Ellison, David W.
AU - Gajjar, Amar
N1 - Funding Information:
This work was supported by grant CA21765 from the National Institutes of Health and the American Lebanese Syrian Associated Charities (ALSAC).
Publisher Copyright:
© The Author(s) 2019.
PY - 2019/10/9
Y1 - 2019/10/9
N2 - Background. This report documents the clinical characteristics, molecular grouping, and outcome of young children with ependymoma treated prospectively on a clinical trial. Methods. Fifty-four children (aged ≤3 y) with newly diagnosed ependymoma were treated on the St Jude Young Children 07 (SJYC07) trial with maximal safe surgical resection, 4 cycles of systemic chemotherapy, consolidation therapy using focal conformal radiation therapy (RT) (5-mm clinical target volume), and 6 months of oral maintenance chemotherapy. Molecular groups were determined by tumor DNA methylation using Infinium Methylation EPIC BeadChip and profiled on the German Cancer Research Center/Molecular Neuropathology 2.0 classifier. Results. One of the 54 study patients had metastases (cerebrospinal fluid positive) at diagnosis. Gross or neartotal resection was achieved in 48 (89%) patients prior to RT. At a median follow-up of 4.4 years (range, 0.2-10.3 y), 4-year progression-free survival (PFS) was 75.1% ±7.2%, and overall survival was 92.6% ±4.4%. The molecular groups showed no significant difference in PFS (4-year estimates: Posterior fossa ependymoma group A [PF-EPN-A; 42/54], 71.2% ±8.3%; supratentorial ependymoma positive for v-rel avian reticuloendotheliosis viral oncogene homolog A [ST-EPN-RELA; 8/54], 83.3% ±17.0%; and supratentorial ependymoma positive for Yes-associated protein [4/54], 100%, P = 0.22). Subtotal resection prior to RT was associated with an inferior PFS compared with gross or near-total resection (4-year PFS: 41.7% ±22.5% vs 79.0% ±7.1%, P = 0.024), as was PF-EPN-A group with 1q gain (P = 0.05). Histopathologic grading was not associated with outcomes (classic vs anaplastic; P = 0.89). Conclusions. In this prospectively treated cohort of young children with ependymoma, ST-EPN-RELA tumors had a more favorable outcome than reported from retrospective data. Histologic grade did not impact outcome. PF-EPN-A with 1q gain and subtotal resection were associated with inferior outcomes.
AB - Background. This report documents the clinical characteristics, molecular grouping, and outcome of young children with ependymoma treated prospectively on a clinical trial. Methods. Fifty-four children (aged ≤3 y) with newly diagnosed ependymoma were treated on the St Jude Young Children 07 (SJYC07) trial with maximal safe surgical resection, 4 cycles of systemic chemotherapy, consolidation therapy using focal conformal radiation therapy (RT) (5-mm clinical target volume), and 6 months of oral maintenance chemotherapy. Molecular groups were determined by tumor DNA methylation using Infinium Methylation EPIC BeadChip and profiled on the German Cancer Research Center/Molecular Neuropathology 2.0 classifier. Results. One of the 54 study patients had metastases (cerebrospinal fluid positive) at diagnosis. Gross or neartotal resection was achieved in 48 (89%) patients prior to RT. At a median follow-up of 4.4 years (range, 0.2-10.3 y), 4-year progression-free survival (PFS) was 75.1% ±7.2%, and overall survival was 92.6% ±4.4%. The molecular groups showed no significant difference in PFS (4-year estimates: Posterior fossa ependymoma group A [PF-EPN-A; 42/54], 71.2% ±8.3%; supratentorial ependymoma positive for v-rel avian reticuloendotheliosis viral oncogene homolog A [ST-EPN-RELA; 8/54], 83.3% ±17.0%; and supratentorial ependymoma positive for Yes-associated protein [4/54], 100%, P = 0.22). Subtotal resection prior to RT was associated with an inferior PFS compared with gross or near-total resection (4-year PFS: 41.7% ±22.5% vs 79.0% ±7.1%, P = 0.024), as was PF-EPN-A group with 1q gain (P = 0.05). Histopathologic grading was not associated with outcomes (classic vs anaplastic; P = 0.89). Conclusions. In this prospectively treated cohort of young children with ependymoma, ST-EPN-RELA tumors had a more favorable outcome than reported from retrospective data. Histologic grade did not impact outcome. PF-EPN-A with 1q gain and subtotal resection were associated with inferior outcomes.
KW - 1q gain
KW - Chemotherapy
KW - Clinical target volume
KW - Ependymoma groups
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U2 - 10.1093/neuonc/noz069
DO - 10.1093/neuonc/noz069
M3 - Article
C2 - 30976811
AN - SCOPUS:85073084855
SN - 1522-8517
VL - 21
SP - 1319
EP - 1330
JO - Neuro-oncology
JF - Neuro-oncology
IS - 10
ER -