Clinical Management of Embryonal Tumor with Multilayered Rosettes: The CCMC Experience
Abstract
:1. Introduction
2. Patients and Methods
2.1. Patients
2.2. Treatment
2.3. Response and Toxicity
3. Result
3.1. Patients
3.2. Treatment and Toxicity
3.3. Treatment Response and Clinical Outcome
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Louis, D.N.; Perry, A.; Reifenberger, G.; Von Deimling, A.; Figarella-Branger, D.; Cavenee, W.K.; Ohgaki, H.; Wiestler, O.D.; Kleihues, P.; Ellison, D.W. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: A summary. Acta Neuropathol. 2016, 131, 803–820. [Google Scholar] [CrossRef] [Green Version]
- Korshunov, A.; Remke, M.; Gessi, M.; Ryzhova, M.; Hielscher, T.; Witt, H.; Tobias, V.; Buccoliero, A.M.; Sardi, I.; Gardiman, M.P.; et al. Focal genomic amplification at 19q13.42 comprises a powerful diagnostic marker for embryonal tumors with ependymoblastic rosettes. Acta Neuropathol. 2010, 120, 253–260. [Google Scholar] [CrossRef]
- Spence, T.; Sin-Chan, P.; Picard, D.; Barszczyk, M.; Hoss, K.; Lu, M.; Kim, S.-K.; Ra, Y.-S.; Nakamura, H.; Fangusaro, J.; et al. CNS-PNETs with C19MC amplification and/or LIN28 expression comprise a distinct histogenetic diagnostic and therapeutic entity. Acta Neuropathol. 2014, 128, 291–303. [Google Scholar] [CrossRef] [Green Version]
- Louis, D.N.; Perry, A.; Wesseling, P.; Brat, D.J.; Cree, I.A.; Figarella-Branger, D.; Hawkins, C.; Ng, H.K.; Pfister, S.M.; Reifenberger, G.; et al. The 2021 WHO Classification of Tumors of the Central Nervous System: A summary. Neuro Oncol. 2021, 23, 1231–1251. [Google Scholar] [CrossRef]
- Mayr, L.; Gojo, J.; Peyrl, A.; Azizi, A.A.; Stepien, N.M.; Pletschko, T.; Czech, T.; Dorfer, C.; Lambo, S.; Dieckmann, K.; et al. Potential Importance of Early Focal Radiotherapy Following Gross Total Resection for Long-Term Survival in Children with Embryonal Tumors With Multilayered Rosettes. Front. Oncol. 2020, 10, 584681. [Google Scholar] [CrossRef] [PubMed]
- Juhnke, B.-O.; Gessi, M.; Gerber, N.U.; Friedrich, C.; Mynarek, M.; von Bueren, A.O.; Haberler, C.; Schüller, U.; Kortmann, R.-D.; Timmermann, B.; et al. Treatment of embryonal tumors with multilayered rosettes with carboplatin/etoposide induction and high-dose chemotherapy within the prospective P-HIT trial. Neuro Oncol. 2021, 24, 127–137. [Google Scholar] [CrossRef] [PubMed]
- Lambo, S.; Von Hoff, K.; Korshunov, A.; Pfister, S.M.; Kool, M. ETMR: A tumor entity in its infancy. Acta Neuropathol. 2020, 140, 249–266. [Google Scholar] [CrossRef] [PubMed]
- Gállego Pérez-Larraya, J.; Lahutte, M.; Petrirena, G.; Reyes-Botero, G.; González-Aguilar, A.; Houillier, C.; Guillevin, R.; Sanson, M.; Hoang-Xuan, K.; Delattre, J.Y. Response assessment in recurrent glioblastoma treated with irinotecan-bevacizumab: Comparative analysis of the Macdonald, RECIST, RANO, and RECIST + F criteria. Neuro Oncol. 2012, 14, 667–673. [Google Scholar] [CrossRef]
- Dueck, A.C.; Mendoza, T.R.; Mitchell, S.A.; Reeve, B.B.; Castro, K.M.; Rogak, L.J.; Atkinson, T.M.; Bennett, A.V.; Denicoff, A.M.; O’Mara, A.M.; et al. Validity and Reliability of the US National Cancer Institute’s Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). JAMA Oncol. 2015, 1, 1051–1059. [Google Scholar] [CrossRef] [Green Version]
- Korshunov, A.; Sturm, D.; Ryzhova, M.; Hovestadt, V.; Gessi, M.; Jones, D.T.W.; Remke, M.; Northcott, P.; Perry, A.; Picard, D.; et al. Embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma, and medulloepithelioma share molecular similarity and comprise a single clinicopathological entity. Acta Neuropathol. 2013, 128, 279–289. [Google Scholar] [CrossRef]
- Korshunov, A.; Ryzhova, M.; Jones, D.T.W.; Northcott, P.A.; van Sluis, P.; Volckmann, R.; Koster, J.; Versteeg, R.; Cowdrey, C.; Perry, A.; et al. LIN28A immunoreactivity is a potent diagnostic marker of embryonal tumor with multilayered rosettes (ETMR). Acta Neuropathol. 2012, 124, 875–881. [Google Scholar] [CrossRef] [Green Version]
- Uro-Coste, E.; Masliah-Planchon, J.; Siegfried, A.; Blanluet, M.; Lambo, S.; Kool, M.; Roujeau, T.; Boetto, S.; Palenzuela, G.; Bertozzi, A.-I.; et al. ETMR-like infantile cerebellar embryonal tumors in the extended morphologic spectrum of DICER1-related tumors. Acta Neuropathol. 2018, 137, 175–177. [Google Scholar] [CrossRef] [PubMed]
- Dhall, G.; Grodman, H.; Ji, L.; Sands, S.; Gardner, S.; Dunkel, I.J.; McCowage, G.B.; Diez, B.; Allen, J.C.; Gopalan, A.; et al. Outcome of children less than three years old at diagnosis with non-metastatic medulloblastoma treated with chemotherapy on the “Head Start” I and II protocols. Pediatr. Blood Cancer 2008, 50, 1169–1175. [Google Scholar] [CrossRef]
- Odagiri, K.; Omura, M.; Hata, M.; Aida, N.; Niwa, T.; Goto, H.; Ito, S.; Adachi, M.; Yoshida, H.; Yuki, H.; et al. Treatment outcomes and late toxicities in patients with embryonal central nervous system tumors. Radiat. Oncol. 2014, 9, 201. [Google Scholar] [CrossRef] [Green Version]
- Raghuram, N.; Khan, S.; Mumal, I.; Bouffet, E.; Huang, A. Embryonal tumors with multi-layered rosettes: A disease of dysregulated miRNAs. J. Neuro Oncol. 2020, 150, 63–73. [Google Scholar] [CrossRef]
- Horwitz, M.; Dufour, C.; Leblond, P.; Bourdeaut, F.; Faure-Conter, C.; Bertozzi, A.I.; Delisle, M.B.; Palenzuela, G.; Jouvet, A.; Scavarda, D.; et al. Embryonal tumors with multilayered rosettes in children: The SFCE experience. Child’s Nerv. Syst. 2016, 32, 299–305. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jaramillo, S.; Grosshans, D.R.; Philip, N.; Varan, A.; Akyüz, C.; McAleer, M.F.; Mahajan, A.; McGovern, S.L. Radiation for ETMR: Literature review and case series of patients treated with proton therapy. Clin. Transl. Radiat. Oncol. 2018, 15, 31–37. [Google Scholar] [CrossRef] [Green Version]
- Khan, S.; Solano-Paez, P.; Suwal, T.; Lu, M.; Al-Karmi, S.; Ho, B.; Mumal, I.; Shago, M.; Hoffman, L.M.; Dodgshun, A.; et al. Clinical phenotypes and prognostic features of embryonal tumours with multi-layered rosettes: A Rare Brain Tumor Registry study. Lancet Child Adolesc. Health 2021, 5, 800–813. [Google Scholar] [CrossRef]
- Kleinman, C.; Gerges, N.; Papillon-Cavanagh, S.; Sin-Chan, P.; Pramatarova, A.; Quang, D.-A.K.; Adoue, V.; Busche, S.; Caron, M.; Djambazian, H.; et al. Fusion of TTYH1 with the C19MC microRNA cluster drives expression of a brain-specific DNMT3B isoform in the embryonal brain tumor ETMR. Nat. Genet. 2013, 46, 39–44. [Google Scholar] [CrossRef] [PubMed]
- Hanson, D.; Hoffman, L.M.; Nagabushan, S.; Goumnerova, L.C.; Rathmann, A.; Vogel, T.; Ziegler, D.S.; Chi, S. A modified IRS-III chemotherapy regimen leads to prolonged survival in children with embryonal tumor with multilayer rosettes. Neuro Oncol. Adv. 2020, 2, vdaa120. [Google Scholar] [CrossRef] [PubMed]
- Schmidt, C.; Schubert, A.N.; Brabetz, S.; Mack, N.; Schwalm, B.; Chan, A.J.; Selt, F.; Herold-Mende, C.; Witt, O.; Milde, T.; et al. Preclinical drug screen reveals topotecan, actinomycin D, and volasertib as potential new therapeutic candidates for ETMR brain tumor patients. Neuro Oncol. 2017, 19, 1607–1617. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Neumann, J.E.; Wefers, A.K.; Lambo, S.; Bianchi, E.; Bockstaller, M.; Dorostkar, M.M.; Meister, V.; Schindler, P.; Korshunov, A.; Von Hoff, K.; et al. A mouse model for embryonal tumors with multilayered rosettes uncovers the therapeutic potential of Sonic-hedgehog inhibitors. Nat. Med. 2017, 23, 1191–1202. [Google Scholar] [CrossRef]
Drug | Dose | Day |
---|---|---|
Cisplatin (CDDP) | 105 mg/m2 | D1 |
Vincristine (VCR) | 1.5 mg/m2 (Dmax = 2 mg) | D1, 8, 15 (The first three cycles) |
Etoposide (VP-16) | 120 mg/m2 | D2, 3 |
Cyclophosphamide (CTX) | 2000 mg/m2 | D2, 3 |
High-dose methotrexate (HD-MTX) | 12 g/m2 | D4 |
Patient | Sex | Age (Months) | Tumor Site | Clinical Symptoms | Tumor Size (cm3) | C19MC Amplification | Resection | Cycles of Chemotherapy | Radiotherapy | Myelosuppression | Response | Outcome (Months) |
---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | Female | 17 | The frontal temporal lobe | Limb weakness, vomiting | 7.3 × 7.2 × 6.8 | Yes | CTR | 5 | No | III | CR | NED (19) |
2 | Male | 16 | The fourth ventricle | Walking instability | 3.8 × 3.6 × 5.3 | No | CTR | 5 | No | IV | CR | NED (14) |
3 | Male | 25 | The fourth ventricle | Walking instability | 6.0 × 6.0 × 3.8 | Yes | STR | 5 | Yes | IV | PR | AWD (24) |
4 | Male | 66 | Cavernous sinus and slope | Headache, vomiting | 1.6 × 2.7 × 4.2 | Yes | GTR | 2 | No | IV | PD | DOC (18) |
5 | Male | 21 | The temporal lobe | Drowsiness, vomiting, convulsions | 6.1 × 5.9 × 3.0 | Yes | GTR | 2 | No | IV | PD | DOD (6) |
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Li, Z.; Wu, Z.; Dong, Y.; Zhang, D. Clinical Management of Embryonal Tumor with Multilayered Rosettes: The CCMC Experience. Children 2022, 9, 1560. https://doi.org/10.3390/children9101560
Li Z, Wu Z, Dong Y, Zhang D. Clinical Management of Embryonal Tumor with Multilayered Rosettes: The CCMC Experience. Children. 2022; 9(10):1560. https://doi.org/10.3390/children9101560
Chicago/Turabian StyleLi, Zengyan, Zhiming Wu, Youhong Dong, and Dongdong Zhang. 2022. "Clinical Management of Embryonal Tumor with Multilayered Rosettes: The CCMC Experience" Children 9, no. 10: 1560. https://doi.org/10.3390/children9101560
APA StyleLi, Z., Wu, Z., Dong, Y., & Zhang, D. (2022). Clinical Management of Embryonal Tumor with Multilayered Rosettes: The CCMC Experience. Children, 9(10), 1560. https://doi.org/10.3390/children9101560