Journal of Clinical Pediatrics >
Research progress on characterization and therapeutics for recurrent medulloblastoma in children
Received date: 2022-08-15
Online published: 2023-10-08
Medulloblastoma (MB) is a common intracranial malignancy in children with a high recurrence rate despite standardized multimodal initial treatment. The prognosis of recurrent children is very poor even after intensive treatment. In recent years, the in-depth understanding of the clinical and biological characteristics of MB recurrence can guide the clinical design of relevant treatment strategies and implement of clinical trials. This paper reviews the research progress of the above contents, hoping to promote the speed of its clinical transformation and application, and finally benefit the clinical practice.
Key words： medulloblastoma; recurrent; therapy; child
Zaiyu Reviewer: ZHANG , Yuxin WU , Ping Reviser: LIANG . Research progress on characterization and therapeutics for recurrent medulloblastoma in children[J]. Journal of Clinical Pediatrics, 2023 , 41(10) : 708 -714 . DOI: 10.12372/jcp.2023.22e1112
| [1] | Ostrom QT, Cioffi G, Waite K, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2014-2018[J]. Neuro Oncol, 2021, 23(12 Suppl 2): iii1-iii105. |
| [2] | Louis DN, Perry A, Wesseling P, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary[J]. Neuro Oncol, 2021, 23(8): 1231-1251. |
| [3] | Mynarek M, von Hoff K, Pietsch T, et al. Nonmetastatic medulloblastoma of early childhood: results from the prospective clinical trial HIT-2000 and an extended validation cohort[J]. J Clin Oncol, 2020, 38(18): 2028-2040. |
| [4] | Sabel M, Fleischhack G, Tippelt S, et al. Relapse patterns and outcome after relapse in standard risk medulloblastoma: a report from the HIT-SIOP-PNET4 study[J]. J Neurooncol, 2016, 129(3): 515-524. |
| [5] | Kumar R, Smith KS, Deng M, et al. Clinical outcomes and patient-matched molecular composition of relapsed medulloblastoma[J]. J Clin Oncol, 2021, 39(7): 807-821. |
| [6] | Müller K, Mynarek M, Zwiener I, et al. Postponed is not canceled: role of craniospinal radiation therapy in the management of recurrent infant medulloblastoma--an experience from the HIT-REZ 1997 & 2005 studies[J]. Int J Radiat Oncol Biol Phys, 2014, 88(5): 1019-1024. |
| [7] | Levy AS, Krailo M, Chi S, et al. Temozolomide with irinotecan versus temozolomide, irinotecan plus bevacizumab for recurrent medulloblastoma of childhood: report of a COG randomized phase II screening trial[J]. Pediatr Blood Cancer, 2021, 68(8): e29031. |
| [8] | Gaab C, Adolph JE, Tippelt S, et al. Local and systemic therapy of recurrent medulloblastomas in children and adolescents: results of the P-HIT-REZ 2005 study[J]. Cancers (Basel), 2022, 14(3):471. |
| [9] | Gajjar A, Chintagumpala M, Ashley D, et al. Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial[J]. Lancet Oncol, 2006, 7(10): 813-820. |
| [10] | Lannering B, Rutkowski S, Doz F, et al. Hyperfractionated versus conventional radiotherapy followed by chemo-therapy in standard-risk medulloblastoma: results from the randomized multicenter HIT-SIOP PNET 4 trial[J]. J Clin Oncol, 2012, 30(26): 3187-3193. |
| [11] | Dhall G, Grodman H, Ji L, 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[J]. Pediatr Blood Cancer, 2008, 50(6): 1169-1175. |
| [12] | von Bueren AO, von Hoff K, Pietsch T, et al. Treatment of young children with localized medulloblastoma by chemotherapy alone: results of the prospective, multicenter trial HIT 2000 confirming the prognostic impact of histology[J]. Neuro Oncol, 2011, 13(6): 669-679. |
| [13] | Ashley DM, Merchant TE, Strother D, et al. Induction chemotherapy and conformal radiation therapy for very young children with nonmetastatic medulloblastoma: children’s oncology group study P9934[J]. J Clin Oncol, 2012, 30(26): 3181-3186. |
| [14] | Robinson GW, Rudneva VA, Buchhalter I, et al. Risk-adapted therapy for young children with medulloblastoma (SJYC07): therapeutic and molecular outcomes from a multicentre, phase 2 trial[J]. Lancet Oncol, 2018, 19(6): 768-784. |
| [15] | Johnston DL, Keene D, Strother D, et al. Survival following tumor recurrence in children with medullo-blastoma[J]. J Pediatr Hematol Oncol, 2018, 40(3): e159-e163. |
| [16] | Nobre L, Zapotocky M, Khan S, et al. Pattern of relapse and treatment response in WNT-activated medulloblastoma[J]. Cell Rep Med, 2020, 1(3):100038 |
| [17] | Huybrechts S, Le Teuff G, Tauziède-Espariat A, et al. Prognostic clinical and biologic features for overall survival after relapse in childhood medulloblastoma[J]. Cancers (Basel), 2020, 13(1):53. |
| [18] | Koschmann C, Bloom K, Upadhyaya S, et al. Survival after relapse of medulloblastoma[J]. J Pediatr Hematol Oncol, 2016, 38(4): 269-273. |
| [19] | Huang PI, Lin SC, Lee YY, et al. Large cell/anaplastic medulloblastoma is associated with poor prognosis-a retrospective analysis at a single institute[J]. Childs Nerv Syst, 2017, 33(8): 1285-1294. |
| [20] | Aboian MS, Kline CN, Li Y, et al. Early detection of recurrent medulloblastoma: the critical role of diffusion-weighted imaging[J]. Neurooncol Pract, 2018, 5(4): 234-240. |
| [21] | Grassberger C, Shinnick D, Yeap BY, et al. Circulating lymphocyte counts early during radiation therapy are associated with recurrence in pediatric medulloblastoma[J]. Int J Radiat Oncol Biol Phys, 2021, 110(4): 1044-1052. |
| [22] | Du S, Yang S, Zhao X, et al. Clinical characteristics and outcome of children with relapsed medulloblastoma: a retrospective study at a single center in China[J]. J Pediatr Hematol Oncol, 2018, 40(8): 598-604. |
| [23] | Hill RM, Kuijper S, Lindsey JC, et al. Combined MYC and P53 defects emerge at medulloblastoma relapse and define rapidly progressive, therapeutically targetable disease[J]. Cancer cell, 2015, 27(1): 72-84. |
| [24] | Richardson S, Hill RM, Kui C, et al. Emergence and maintenance of actionable genetic drivers at medulloblastoma relapse[J]. Neuro Oncol, 2022, 24(1): 153-165. |
| [25] | Gajjar A, Robinson GW, Smith KS, et al. Outcomes by clinical and molecular features in children with medulloblastoma treated with risk-adapted therapy: results of an international phase III trial (SJMB03)[J]. J Clin Oncol, 2021, 39(7): 822-835. |
| [26] | Hill RM, Richardson S, Schwalbe EC, et al. Time, pattern, and outcome of medulloblastoma relapse and their association with tumour biology at diagnosis and therapy: a multicentre cohort study[J]. Lancet Child Adolesc Health, 2020, 4(12): 865-874. |
| [27] | Ricklefs FL, Fritzsche F, Winkler B, et al. Relapse of a group 4 medulloblastoma after 18 years as proven by histology and DNA methylation profiling[J]. Childs Nerv Syst, 2019, 35(6): 1029-1033. |
| [28] | Tsang DS, Sarhan N, Ramaswamy V, et al. Re-irradiation for children with recurrent medulloblastoma in Toronto, Canada: a 20-year experience[J]. Neuro-oncol, 2019, 145(1): 107-114. |
| [29] | Baroni LV, Freytes C, Fernández Ponce N, et al. Craniospinal irradiation as part of re-irradiation for children with recurrent medulloblastoma[J]. J Neurooncol, 2021, 155(1): 53-61. |
| [30] | Phi JH, Park AK, Lee S, et al. Genomic analysis reveals secondary glioblastoma after radiotherapy in a subset of recurrent medulloblastomas[J]. Acta Neuropathol, 2018, 135(6): 939-953. |
| [31] | Zhao M, Wang X, Fu X, et al. Bevacizumab and stereotactic radiosurgery achieved complete response for pediatric recurrent medulloblastoma[J]. J Cancer Res Ther, 2018, 14(Supplement): S789-S792. |
| [32] | Rao AD, Rashid AS, Chen Q, et al. Reirradiation for recurrent pediatric central nervous system malignancies: a multi-institutional review[J]. Int J Radiat Oncol Biol Phys, 2017, 99(3): 634-641. |
| [33] | Napieralska A, Br?clik I, Radwan M, et al. Radiosurgery or hypofractionated stereotactic radiotherapy after craniospinal irradiation in children and adults with medulloblastoma and ependymoma[J]. Childs Nerv Syst, 2019, 35(2): 267-275. |
| [34] | Osorio DS, Dunkel IJ, Cervone KA, et al. Tandem thiotepa with autologous hematopoietic cell rescue in patients with recurrent, refractory, or poor prognosis solid tumor malignancies[J]. Pediatr Blood Cancer, 2018, 65(1). doi: 10.1002/pbc.26776. |
| [35] | Slavc I, Peyrl A, Gojo J, et al. MMbcl-43. recurrent medulloblastoma - long-term survival with a “memmat” based antiangiogenic approach[J]. Neuro-oncology, 2020, 22(Supplement_3): iii397-iii397. |
| [36] | Pajtler KW, Tippelt S, Siegler N, et al. Intraventricular etoposide safety and toxicity profile in children and young adults with refractory or recurrent malignant brain tumors[J]. J Neurooncol, 2016, 128(3): 463-471. |
| [37] | Bonney PA, Santucci JA, Maurer AJ, et al. Dramatic response to temozolomide, irinotecan, and bevacizumab for recurrent medulloblastoma with widespread osseous metastases[J]. J Clin Neurosci, 2016, 26: 161-163. |
| [38] | Schiavetti A, Varrasso G, Mollace MG, et al. Bevaci-zumab-containing regimen in relapsed/progressed brain tumors: a single-institution experience[J]. Childs Nerv Syst, 2019, 35(6): 1007-1012. |
| [39] | Robinson GW, Orr BA, Wu G, et al. Vismodegib exerts targeted efficacy against recurrent sonic hedgehog-subgroup medulloblastoma: results from phase II pediatric brain tumor consortium studies PBTC-025B and PBTC-032[J]. J Clin Oncol, 2015, 33(24): 2646-2654. |
| [40] | Kieran MW, Chisholm J, Casanova M, et al. Phase I study of oral sonidegib (LDE225) in pediatric brain and solid tumors and a phase II study in children and adults with relapsed medulloblastoma[J]. Neuro Oncol, 2017, 19(11): 1542-1552. |
| [41] | Pereira V, Torrejon J, Kariyawasam D, et al. Clinical and molecular analysis of smoothened inhibitors in sonic hedgehog medulloblastoma[J]. Neurooncol Adv, 2021, 3(1): vdab097. |
| [42] | Cook Sangar ML, Genovesi LA, Nakamoto MW, et al. Inhibition of CDK4/6 by palbociclib significantly extends survival in medulloblastoma patient-derived xenograft mouse models[J]. Clin Cancer Res, 2017, 23(19): 5802-5813. |
| [43] | Shapiro GI. Cyclin-dependent kinase pathways as targets for cancer treatment[J]. J Clin Oncol, 2006, 24(11): 1770-1783. |
| [44] | Burkhart DL, Sage J. Cellular mechanisms of tumour suppression by the retinoblastoma gene[J]. Nat Rev Cancer, 2008, 8(9): 671-682. |
| [45] | Bockmayr M, Mohme M, Klauschen F, et al. Subgroup-specific immune and stromal microenvironment in medulloblastoma[J]. Oncoimmunology, 2018, 7(9): e1462430. |
| [46] | Diao S, Gu C, Zhang H, et al. Immune cell infiltration and cytokine secretion analysis reveal a non-inflammatory microenvironment of medulloblastoma[J]. Oncol Lett, 2020, 20(6): 397. |
| [47] | Pham CD, Flores C, Yang C, et al. Differential immune microenvironments and response to immune checkpoint blockade among molecular subtypes of murine medulloblastoma[J]. Clin Cancer Res, 2016, 22(3): 582-595. |
| [48] | Donovan LK, Delaidelli A, Joseph SK, et al. Locoregional delivery of CAR T cells to the cerebrospinal fluid for treatment of metastatic medulloblastoma and ependymoma[J]. Nat Med, 2020, 26(5): 720-731. |
| [49] | Castriconi R, Dondero A, Negri F, et al. Both CD133+ and CD133- medulloblastoma cell lines express ligands for triggering NK receptors and are susceptible to NK-mediated cytotoxicity[J]. Eur J Immunol, 2007, 37(11): 3190-3196. |
| [50] | Khatua S, Cooper LJN, Sandberg DI, et al. Phase I study of intraventricular infusions of autologous ex vivo expanded NK cells in children with recurrent medulloblastoma and ependymoma[J]. Neuro Oncol, 2020, 22(8): 1214-1225. |
| [51] | Kramer K, Pandit-Taskar N, Humm JL, et al. A phase II study of radioimmunotherapy with intraventricular (131) I-3F8 for medulloblastoma[J]. Pediatr Blood Cancer, 2018, 65(1):10.1002. |
| [52] | Liu Y, Yuelling LW, Wang Y, et al. Astrocytes promote medulloblastoma progression through hedgehog secretion[J]. Cancer Res, 2017, 77(23): 6692-6703. |
| [53] | Zhang L, He X, Liu X, et al. Single-Cell transcriptomics in medulloblastoma reveals tumor-initiating progenitors and oncogenic cascades during tumorigenesis and relapse[J]. Cancer Cell, 2019, 36(3): 302-318. |
| [54] | Yao M, Ventura PB, Jiang Y, et al. Astrocytic trans-differentiation completes a multicellular paracrine feedback loop required for medulloblastoma tumor growth[J]. Cell, 2020, 180(3): 502-520. |
| [55] | Singh SK, Hawkins C, Clarke ID, et al. Identification of human brain tumour initiating cells[J]. Nature, 2004, 432(7015): 396-401. |
| [56] | Garg N, Bakhshinyan D, Venugopal C, et al. CD133(+) brain tumor-initiating cells are dependent on STAT3 signaling to drive medulloblastoma recurrence[J]. Oncogene, 2017, 36(5): 606-617. |
| [57] | Bakhshinyan D, Adile AA, Liu J, et al. Temporal profiling of therapy resistance in human medulloblastoma identifies novel targetable drivers of recurrence[J]. Sci Adv, 2021, 7(50): eabi5568. |
| [58] | Leung C, Lingbeek M, Shakhova O, et al. Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas[J]. Nature, 2004, 428(6980): 337-341. |
| [59] | Bakhshinyan D, Venugopal C, Adile AA, et al. BMI1 is a therapeutic target in recurrent medulloblastoma[J]. Oncogene, 2019, 38(10): 1702-1716. |
| [60] | Guo D, Wang Y, Cheng Y, et al. Tumor cells generate astrocytelike cells that contribute to SHH-driven medulloblastoma relapse[J]. J Exp Med, 2021, 218(9): e20202350. |
/
| 〈 |
|
〉 |
