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A phase I/II study of ribociclib following radiation therapy in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG)

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Abstract

Purpose

Cyclin-dependent kinase-retinoblastoma (CDK-RB) pathway is dysregulated in some diffuse intrinsic pontine gliomas (DIPG). We evaluated safety, feasibility, and early efficacy of the CDK4/6-inhibitor ribociclib, administered following radiotherapy in newly-diagnosed DIPG patients.

Methods

Following radiotherapy, eligible patients received ribociclib in 28-day cycles (350 mg/m2; 21 days on/7 days off). Feasibility endpoints included tolerability for at least 6 courses, and a less than 2-week delay in restarting therapy after 1 dose reduction. Early efficacy was measured by 1-year and median overall survival (OS). Patient/parent-by-proxy reported outcomes measurement information system (PROMIS) assessments were completed prospectively.

Results

The study included 10 evaluable patients, 9 DIPG and 1 diffuse midline glioma (DMG)—all 3.7 to 19.8 years of age. The median number of courses was 8 (range 3–14). Three patients required dose reduction for grade-4 neutropenia, and 1 discontinued therapy for hematological toxicity following course 4. The most common grade-3/4 toxicity was myelosuppression. After 2 courses, MRI evaluations in 4 patients revealed increased necrotic volume, associated with new neurological symptoms in 3 patients. The 1-year and median OS for DIPG was 89% and 16.1 months (range 10–30), respectively; the DMG patient died at 6 months post-diagnosis. Five patients donated brain tissue and tumor; 3 were RB+ .

Conclusions

Ribociclib administered following radiotherapy is feasible in DIPG and DMG. Increased tumor necrosis may represent a treatment effect. These data warrant further prospective volumetric analyses of tumors with necrosis. Feasibility and stabilization findings support further investigation of ribociclib in combination therapies.

Trial registration

NCT02607124.

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Data availability

All data generated or analyzed during this study are included in this published article.

References

  1. Hargrave D, Bartels U, Bouffet E (2006) Diffuse brainstem glioma in children: critical review of clinical trials. Lancet Oncol 7:241–248. https://doi.org/10.1016/S1470-2045(06)70615-5

    Article  Google Scholar 

  2. Jansen MH, van Vuurden DG, Vandertop WP, Kaspers GJ (2012) Diffuse intrinsic pontine gliomas: a systematic update on clinical trials and biology. Cancer Treat Rev 38:27–35. https://doi.org/10.1016/j.ctrv.2011.06.007

    Article  CAS  Google Scholar 

  3. Karremann M, Gielen GH, Hoffmann M, Wiese M, Colditz N, Warmuth-Metz M, Bison B, Claviez A, van Vuurden DG, von Bueren AO, Gessi M, Kuhnle I, Hans VH, Benesch M, Sturm D, Kortmann RD, Waha A, Pietsch T, Kramm CM (2018) Diffuse high-grade gliomas with H3 K27M mutations carry a dismal prognosis independent of tumor location. Neuro-Oncology 20:123–131. https://doi.org/10.1093/neuonc/nox149

    Article  CAS  Google Scholar 

  4. Shapiro GI (2006) Cyclin-dependent kinase pathways as targets for cancer treatment. J Clin Oncol 24:1770–1783. https://doi.org/10.1200/JCO.2005.03.7689

    Article  CAS  Google Scholar 

  5. Wu G, Broniscer A, McEachron TA, Lu C, Paugh BS, Becksfort J, Qu C, Ding L, Huether R, Parker M, Zhang J, Gajjar A, Dyer MA, Mullighan CG, Gilbertson RJ, Mardis ER, Wilson RK, Downing JR, Ellison DW, Baker SJ, Project SJCsRHWUPCG (2012) Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet 44:251–253. https://doi.org/10.1038/ng.1102

    Article  CAS  Google Scholar 

  6. Schwartzentruber J, Korshunov A, Liu XY, Jones DT, Pfaff E, Jacob K, Sturm D, Fontebasso AM, Quang DA, Tönjes M, Hovestadt V, Albrecht S, Kool M, Nantel A, Konermann C, Lindroth A, Jäger N, Rausch T, Ryzhova M, Korbel JO, Hielscher T, Hauser P, Garami M, Klekner A, Bognar L, Ebinger M, Schuhmann MU, Scheurlen W, Pekrun A, Frühwald MC, Roggendorf W, Kramm C, Dürken M, Atkinson J, Lepage P, Montpetit A, Zakrzewska M, Zakrzewski K, Liberski PP, Dong Z, Siegel P, Kulozik AE, Zapatka M, Guha A, Malkin D, Felsberg J, Reifenberger G, von Deimling A, Ichimura K, Collins VP, Witt H, Milde T, Witt O, Zhang C, Castelo-Branco P, Lichter P, Faury D, Tabori U, Plass C, Majewski J, Pfister SM, Jabado N (2012) Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 482:226–231. https://doi.org/10.1038/nature10833

    Article  CAS  Google Scholar 

  7. Buczkowicz P, Hoeman C, Rakopoulos P, Pajovic S, Letourneau L, Dzamba M, Morrison A, Lewis P, Bouffet E, Bartels U, Zuccaro J, Agnihotri S, Ryall S, Barszczyk M, Chornenkyy Y, Bourgey M, Bourque G, Montpetit A, Cordero F, Castelo-Branco P, Mangerel J, Tabori U, Ho KC, Huang A, Taylor KR, Mackay A, Bendel AE, Nazarian J, Fangusaro JR, Karajannis MA, Zagzag D, Foreman NK, Donson A, Hegert JV, Smith A, Chan J, Lafay-Cousin L, Dunn S, Hukin J, Dunham C, Scheinemann K, Michaud J, Zelcer S, Ramsay D, Cain J, Brennan C, Souweidane MM, Jones C, Allis CD, Brudno M, Becher O, Hawkins C (2014) Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations. Nat Genet. https://doi.org/10.1038/ng.2936

    Article  Google Scholar 

  8. Fontebasso AM, Papillon-Cavanagh S, Schwartzentruber J, Nikbakht H, Gerges N, Fiset PO, Bechet D, Faury D, De Jay N, Ramkissoon LA, Corcoran A, Jones DT, Sturm D, Johann P, Tomita T, Goldman S, Nagib M, Bendel A, Goumnerova L, Bowers DC, Leonard JR, Rubin JB, Alden T, Browd S, Geyer JR, Leary S, Jallo G, Cohen K, Gupta N, Prados MD, Carret AS, Ellezam B, Crevier L, Klekner A, Bognar L, Hauser P, Garami M, Myseros J, Dong Z, Siegel PM, Malkin H, Ligon AH, Albrecht S, Pfister SM, Ligon KL, Majewski J, Jabado N, Kieran MW (2014) Recurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma. Nat Genet. https://doi.org/10.1038/ng.2950

    Article  Google Scholar 

  9. Brennan CW, Verhaak RG, McKenna A, Campos B, Noushmehr H, Salama SR, Zheng S, Chakravarty D, Sanborn JZ, Berman SH, Beroukhim R, Bernard B, Wu CJ, Genovese G, Shmulevich I, Barnholtz-Sloan J, Zou L, Vegesna R, Shukla SA, Ciriello G, Yung WK, Zhang W, Sougnez C, Mikkelsen T, Aldape K, Bigner DD, Van Meir EG, Prados M, Sloan A, Black KL, Eschbacher J, Finocchiaro G, Friedman W, Andrews DW, Guha A, Iacocca M, O'Neill BP, Foltz G, Myers J, Weisenberger DJ, Penny R, Kucherlapati R, Perou CM, Hayes DN, Gibbs R, Marra M, Mills GB, Lander E, Spellman P, Wilson R, Sander C, Weinstein J, Meyerson M, Gabriel S, Laird PW, Haussler D, Getz G, Chin L, Network TR (2013) The somatic genomic landscape of glioblastoma. Cell 155:462–477. https://doi.org/10.1016/j.cell.2013.09.034

    Article  CAS  Google Scholar 

  10. Paugh BS, Broniscer A, Qu C, Miller CP, Zhang J, Tatevossian RG, Olson JM, Geyer JR, Chi SN, da Silva NS, Onar-Thomas A, Baker JN, Gajjar A, Ellison DW, Baker SJ (2011) Genome-wide analyses identify recurrent amplifications of receptor tyrosine kinases and cell-cycle regulatory genes in diffuse intrinsic pontine glioma. J Clin Oncol 29:3999–4006. https://doi.org/10.1200/JCO.2011.35.5677

    Article  CAS  Google Scholar 

  11. Taylor KR, Mackay A, Truffaux N, Butterfield YS, Morozova O, Philippe C, Castel D, Grasso CS, Vinci M, Carvalho D, Carcaboso AM, de Torres C, Cruz O, Mora J, Entz-Werle N, Ingram WJ, Monje M, Hargrave D, Bullock AN, Puget S, Yip S, Jones C, Grill J (2014) Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma. Nat Genet. https://doi.org/10.1038/ng.2925

    Article  Google Scholar 

  12. Grill J, Puget S, Andreiuolo F, Philippe C, MacConaill L, Kieran MW (2012) Critical oncogenic mutations in newly diagnosed pediatric diffuse intrinsic pontine glioma. Pediatr Blood Cancer 58:489–491. https://doi.org/10.1002/pbc.24060

    Article  Google Scholar 

  13. Infante JR, Cassier PA, Gerecitano JF, Witteveen PO, Chugh R, Ribrag V, Chakraborty A, Matano A, Dobson JR, Crystal AS, Parasuraman S, Shapiro GI (2016) A phase I study of the cyclin-dependent kinase 4/6 Inhibitor Ribociclib (LEE011) in patients with advanced solid tumors and lymphomas. Clin Cancer Res 22:5696–5705. https://doi.org/10.1158/1078-0432.CCR-16-1248

    Article  CAS  Google Scholar 

  14. Geoerger B, Bourdeaut F, DuBois SG, Fischer M, Geller JI, Gottardo NG, Marabelle A, Pearson ADJ, Modak S, Cash T, Robinson GW, Motta M, Matano A, Bhansali SG, Dobson JR, Parasuraman S, Chi SN (2017) A phase I study of the CDK4/6 inhibitor ribociclib (LEE011) in pediatric patients with malignant rhabdoid tumors, neuroblastoma, and other solid tumors. Clin Cancer Res 23:2433–2441. https://doi.org/10.1158/1078-0432.CCR-16-2898

    Article  CAS  Google Scholar 

  15. Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW (2016) The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131:803–820. https://doi.org/10.1007/s00401-016-1545-1

    Article  Google Scholar 

  16. Irwin DE, Gross HE, Stucky BD, Thissen D, DeWitt EM, Lai JS, Amtmann D, Khastou L, Varni JW, DeWalt DA (2012) Development of six PROMIS pediatrics proxy-report item banks. Health Qual Life Outcomes 10:22. https://doi.org/10.1186/1477-7525-10-22

    Article  Google Scholar 

  17. Muthén LKaM, B.O. (1998–2017) Mplus user’s guide

  18. Warren KE, Patronas N, Aikin AA, Albert PS, Balis FM (2001) Comparison of one-, two-, and three-dimensional measurements of childhood brain tumors. J Natl Cancer Inst 93:1401–1405

    Article  CAS  Google Scholar 

  19. Gilligan LA, DeWire-Schottmiller MD, Fouladi M, DeBlank P, Leach JL (2020) Tumor response assessment in diffuse intrinsic pontine glioma: comparison of semiautomated volumetric, semiautomated linear, and manual linear tumor measurement strategies. AJNR Am J Neuroradiol 41:866–873. https://doi.org/10.3174/ajnr.A6555

    Article  CAS  Google Scholar 

  20. Goldhoff P, Clarke J, Smirnov I, Berger MS, Prados MD, James CD, Perry A, Phillips JJ (2012) Clinical stratification of glioblastoma based on alterations in retinoblastoma tumor suppressor protein (RB1) and association with the proneural subtype. J Neuropathol Exp Neurol 71:83–89. https://doi.org/10.1097/NEN.0b013e31823fe8f1

    Article  CAS  Google Scholar 

  21. Solomon DA, Wood MD, Tihan T, Bollen AW, Gupta N, Phillips JJ, Perry A (2016) Diffuse midline gliomas with histone H3–K27M mutation: a series of 47 cases assessing the spectrum of morphologic variation and associated genetic alterations. Brain Pathol 26:569–580. https://doi.org/10.1111/bpa.12336

    Article  CAS  Google Scholar 

  22. Hoffman LM, DeWire M, Ryall S, Buczkowicz P, Leach J, Miles L, Ramani A, Brudno M, Kumar SS, Drissi R, Dexheimer P, Salloum R, Chow L, Hummel T, Stevenson C, Lu QR, Jones B, Witte D, Aronow B, Hawkins CE, Fouladi M (2016) Spatial genomic heterogeneity in diffuse intrinsic pontine and midline high-grade glioma: implications for diagnostic biopsy and targeted therapeutics. Acta Neuropathol Commun 4:1. https://doi.org/10.1186/s40478-015-0269-0

    Article  CAS  Google Scholar 

  23. McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, Garimella K, Altshuler D, Gabriel S, Daly M, DePristo MA (2010) The Genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res 20:1297–1303. https://doi.org/10.1101/gr.107524.110

    Article  CAS  Google Scholar 

  24. Cibulskis K, Lawrence MS, Carter SL, Sivachenko A, Jaffe D, Sougnez C, Gabriel S, Meyerson M, Lander ES, Getz G (2013) Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nat Biotechnol 31:213–219. https://doi.org/10.1038/nbt.2514

    Article  CAS  Google Scholar 

  25. McLaren W, Gil L, Hunt SE, Riat HS, Ritchie GR, Thormann A, Flicek P, Cunningham F (2016) The ensembl variant effect predictor. Genome Biol 17:122. https://doi.org/10.1186/s13059-016-0974-4

    Article  CAS  Google Scholar 

  26. Sherr CJ, Beach D, Shapiro GI (2016) Targeting CDK4 and CDK6: from discovery to therapy. Cancer Discov 6:353–367. https://doi.org/10.1158/2159-8290.CD-15-0894

    Article  CAS  Google Scholar 

  27. Hoffman LM, Veldhuijzen van Zanten SEM, Colditz N, Baugh J, Chaney B, Hoffmann M, Lane A, Fuller C, Miles L, Hawkins C, Bartels U, Bouffet E, Goldman S, Leary S, Foreman NK, Packer R, Warren KE, Broniscer A, Kieran MW, Minturn J, Comito M, Broxson E, Shih CS, Khatua S, Chintagumpala M, Carret AS, Escorza NY, Hassall T, Ziegler DS, Gottardo N, Dholaria H, Doughman R, Benesch M, Drissi R, Nazarian J, Jabado N, Boddaert N, Varlet P, Giraud G, Castel D, Puget S, Jones C, Hulleman E, Modena P, Giagnacovo M, Antonelli M, Pietsch T, Gielen GH, Jones DTW, Sturm D, Pfister SM, Gerber NU, Grotzer MA, Pfaff E, von Bueren AO, Hargrave D, Solanki GA, Jadrijevic Cvrlje F, Kaspers GJL, Vandertop WP, Grill J, Bailey S, Biassoni V, Massimino M, Calmon R, Sanchez E, Bison B, Warmuth-Metz M, Leach J, Jones B, van Vuurden DG, Kramm CM, Fouladi M (2018) Clinical, radiologic, pathologic, and molecular characteristics of long-term survivors of Diffuse Intrinsic Pontine Glioma (DIPG): a Collaborative Report From the International and European Society for Pediatric Oncology DIPG Registries. J Clin Oncol. https://doi.org/10.1200/JCO.2017.75.9308

    Article  Google Scholar 

  28. Stevens MC, Mahler H, Parkes S (1998) The health status of adult survivors of cancer in childhood. Eur J Cancer 34:694–698

    Article  CAS  Google Scholar 

  29. Landier W, Bhatia S (2008) Cancer survivorship: a pediatric perspective. Oncologist 13:1181–1192. https://doi.org/10.1634/theoncologist.2008-0104

    Article  Google Scholar 

  30. Nandagopal R, Laverdière C, Mulrooney D, Hudson MM, Meacham L (2008) Endocrine late effects of childhood cancer therapy: a report from the Children's Oncology Group. Horm Res 69:65–74. https://doi.org/10.1159/000111809

    Article  CAS  Google Scholar 

  31. Armstrong GT, Liu Q, Yasui Y, Huang S, Ness KK, Leisenring W, Hudson MM, Donaldson SS, King AA, Stovall M, Krull KR, Robison LL, Packer RJ (2009) Long-term outcomes among adult survivors of childhood central nervous system malignancies in the Childhood Cancer Survivor Study. J Natl Cancer Inst 101:946–958. https://doi.org/10.1093/jnci/djp148

    Article  Google Scholar 

  32. Merchant TE, Pollack IF, Loeffler JS (2010) Brain tumors across the age spectrum: biology, therapy, and late effects. Semin Radiat Oncol 20:58–66. https://doi.org/10.1016/j.semradonc.2009.09.005

    Article  Google Scholar 

  33. Rose SR, Schreiber RE, Kearney NS, Lustig RH, Danish RK, Burghen GA, Hudson MM (2004) Hypothalamic dysfunction after chemotherapy. J Pediatr Endocrinol Metab 17:55–66

    Article  Google Scholar 

  34. Merchant TE, Williams T, Smith JM, Rose SR, Danish RK, Burghen GA, Kun LE, Lustig RH (2002) Preirradiation endocrinopathies in pediatric brain tumor patients determined by dynamic tests of endocrine function. Int J Radiat Oncol Biol Phys 54:45–50

    Article  Google Scholar 

  35. Spoudeas HA (2002) Growth and endocrine function after chemotherapy and radiotherapy in childhood. Eur J Cancer 38:1748–1759 (discussion 1760-1741)

    Article  CAS  Google Scholar 

  36. Green DM, Sklar CA, Boice JD, Mulvihill JJ, Whitton JA, Stovall M, Yasui Y (2009) Ovarian failure and reproductive outcomes after childhood cancer treatment: results from the Childhood Cancer Survivor Study. J Clin Oncol 27:2374–2381. https://doi.org/10.1200/JCO.2008.21.1839

    Article  Google Scholar 

  37. Wallace WH, Anderson RA, Irvine DS (2005) Fertility preservation for young patients with cancer: who is at risk and what can be offered? Lancet Oncol 6:209–218. https://doi.org/10.1016/S1470-2045(05)70092-9

    Article  Google Scholar 

  38. DeWire M, Green DM, Sklar CA, Merchant TE, Wallace D, Lin T, Vern-Gross T, Kun LE, Krasin MJ, Boyett JM, Wright KD, Wetmore C, Broniscer A, Gajjar A (2015) Pubertal development and primary ovarian insufficiency in female survivors of embryonal brain tumors following risk-adapted craniospinal irradiation and adjuvant chemotherapy. Pediatr Blood Cancer 62:329–334. https://doi.org/10.1002/pbc.25274

    Article  CAS  Google Scholar 

  39. Bardia A (2015) Triplet therapy with ribociclib, everolimus, and exemestane in postmenopausal women with HR+/HER2- advanced breast cancer. Clin Cancer Res 24(21):5206–5218

    Article  Google Scholar 

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Acknowledgements

We gratefully acknowledge the excellent regulatory support of Dr. Renee Doughman, data management by Nicole O’Connell, and the generosity of the patients and their families for supporting the study.

Funding

This work was financially supported by Novartis Pharmaceuticals, The Cure Starts Now Foundation, Hope for Caroline Foundation, Julian Boivin Courage for Cures Foundation, Abbie's Army, Michael Mosier Defeat DIPG Foundation, Reflections of Grace Foundation, The Cure Starts Now Australia, Brooke Healey Foundation, Soar With Grace Foundation, Jeffrey Thomas Hayden Foundation, Cure Brain Cancer Foundation, The Jones Family Foundation, Musella Foundation, Pray, Hope Believe Foundation, Smiles for Sophie Foundation, Benny's World, Love Chloe Foundation, Aiden's Avengers, A Cure from Caleb Society, The Operation Grace White Foundation, Ryan's Hope, Wayland Villars DIPG Foundation, American Childhood Cancer Organization, Juliana Rose Donnelly Trust, Sheila Jones & Friends, The Ellie Kavalieros DIPG Research Fund, Voices Against Brain Cancer, and The DIPG Collaborative.

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Authors and Affiliations

  1. Division of Oncology, Department of Pediatrics College of Medicine, Brain Tumor Center, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, 3333 Burnet Avenue, MLC 7015, Cincinnati, OH, 45209, USA

    Mariko DeWire, Trent R. Hummel, Ralph Salloum, Peter de Blank, Shiva Senthil Kumar, Rachid Drissi & Maryam Fouladi

  2. Division of Pathology and Laboratory Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Christine Fuller & David Witte

  3. Department of Hematology/Oncology, Dayton Children’s Hospital, Dayton, OH, USA

    Lionel M. L. Chow

  4. Department of Radiation Oncology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Luke Pater & John Breneman

  5. Department of Endocrinology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Sarah Lawson

  6. Department of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Xiaoting Zhu & Phil Dexheimer

  7. Department of Pediatrics, Department of Psychology, College of Medicine University of Cincinnati, College of Arts and Sciences University of Cincinnati, Anderson Center Health Systems Excellence, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Adam C. Carle

  8. Division of Neurosurgery, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Charles B. Stevenson

  9. Department of Biostatistics, Cincinnati, OH, USA

    Adam Lane

  10. Department of Radiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Blaise V. Jones & James L. Leach

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  1. Mariko DeWire
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  2. Christine Fuller
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  3. Trent R. Hummel
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Contributions

Conception and design: MD, MF, and AL. Data collection and assembly: NOC. Data analyses and interpretation: all authors with survival analyses by AL, molecular analyses by XZ, and pathologic analyses by CF. Manuscript writing and editing: MD with critical feedback from all authors. Final approval of manuscript: All authors. Accountable for all aspects of the work: All authors.

Corresponding author

Correspondence to Mariko DeWire.

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DeWire, M., Fuller, C., Hummel, T.R. et al. A phase I/II study of ribociclib following radiation therapy in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG). J Neurooncol 149, 511–522 (2020). https://doi.org/10.1007/s11060-020-03641-2

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