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The role of adjuvant chemotherapy in patients with H3K27 altered diffuse midline gliomas: a multicentric retrospective study

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Abstract

Purpose

Adult Diffuse midline glioma (DMG) is a very rare disease. DMGs are currently treated with radiotherapy and chemotherapy even if only a few retrospective studies assessed the impact on overall survival (OS) of these approaches.

Methods

We carried out an Italian multicentric retrospective study of adult patients with H3K27-altered DMG to assess the effective role of systemic therapy in the treatment landscape of this rare tumor type.

Results

We evaluated 49 patients from 6 Institutions. The median age was 37.3 years (range 20.1–68.3). Most patients received biopsy as primary approach (n = 30, 61.2%) and radiation therapy after surgery (n = 39, 79.6%). 25 (51.0%) of patients received concurrent chemotherapy and 26 (53.1%) patients received adjuvant temozolomide. In univariate analysis, concurrent chemotherapy did not result in OS improvement while adjuvant temozolomide was associated with longer OS (21.2 vs. 9.0 months, HR 0.14, 0.05–0.41, p < 0.001). Multivariate analysis confirmed the role of adjuvant chemotherapy (HR 0.1, 95%CI: 0.03–0.34, p = 0.003). In patients who progressed after radiation and/or chemotherapy the administration of a second-line systemic treatment had a significantly favorable impact on survival (8.0 vs. 3.2 months, HR 0.2, 95%CI 0.1–0.65, p = 0.004).

Conclusion

In our series, adjuvant treatment after radiotherapy can be useful in improving OS of patients with H3K27-altered DMG. When feasible another systemic treatment after treatment progression could be proposed.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, Hawkins C, Ng HK, Pfister SM, Reifenberger G, Soffietti R, von Deimling A, Ellison DW (2021) The 2021 WHO classification of tumors of the Central Nervous System: a summary. Neuro Oncol 23:1231–1251. https://doi.org/10.1093/neuonc/noab106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Dono A, Takayasu T, Ballester LY, Esquenazi Y (2020) Adult diffuse midline gliomas: clinical, radiological, and genetic characteristics. J Clin Neurosci 82:1–8. https://doi.org/10.1016/j.jocn.2020.10.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Ostrom QT, Cioffi G, Waite K, Kruchko C, Barnholtz-Sloan JS (2021) CBTRUS Statistical Report: primary brain and other Central Nervous System tumors diagnosed in the United States in 2014–2018. Neuro Oncol 23:iii1–iii105. https://doi.org/10.1093/neuonc/noab200

    Article  PubMed  PubMed Central  Google Scholar 

  4. Sturm D, Witt H, Hovestadt V, Khuong-Quang DA, Jones DT, Konermann C, Pfaff E, Tönjes M, Sill M, Bender S, Kool M, Zapatka M, Becker N, Zucknick M, Hielscher T, Liu XY, Fontebasso AM, Ryzhova M, Albrecht S, Jacob K, Wolter M, Ebinger M, Schuhmann MU, van Meter T, Frühwald MC, Hauch H, Pekrun A, Radlwimmer B, Niehues T, von Komorowski G, Dürken M, Kulozik AE, Madden J, Donson A, Foreman NK, Drissi R, Fouladi M, Scheurlen W, von Deimling A, Monoranu C, Roggendorf W, Herold-Mende C, Unterberg A, Kramm CM, Felsberg J, Hartmann C, Wiestler B, Wick W, Milde T, Witt O, Lindroth AM, Schwartzentruber J, Faury D, Fleming A, Zakrzewska M, Liberski PP, Zakrzewski K, Hauser P, Garami M, Klekner A, Bognar L, Morrissy S, Cavalli F, Taylor MD, van Sluis P, Koster J, Versteeg R, Volckmann R, Mikkelsen T, Aldape K, Reifenberger G, Collins VP, Majewski J, Korshunov A, Lichter P, Plass C, Jabado N, Pfister SM (2012) Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. Cancer Cell 22:425–437. https://doi.org/10.1016/j.ccr.2012.08.024

    Article  CAS  PubMed  Google Scholar 

  5. Castel D, Philippe C, Calmon R, Le Dret L, Truffaux N, Boddaert N, Pagès M, Taylor KR, Saulnier P, Lacroix L, Mackay A, Jones C, Sainte-Rose C, Blauwblomme T, Andreiuolo F, Puget S, Grill J, Varlet P, Debily MA (2015) Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes. Acta Neuropathol 130:815–827. https://doi.org/10.1007/s00401-015-1478-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Findlay IJ, De Iuliis GN, Duchatel RJ, Jackson ER, Vitanza NA, Cain JE, Waszak SM, Dun MD (2022) Pharmaco-proteogenomic profiling of pediatric diffuse midline glioma to inform future treatment strategies. Oncogene 41:461–475. https://doi.org/10.1038/s41388-021-02102-y

    Article  CAS  PubMed  Google Scholar 

  7. Antin C, Tauziède-Espariat A, Debily MA, Castel D, Grill J, Pagès M, Ayrault O, Chrétien F, Gareton A, Andreiuolo F, Lechapt E, Varlet P (2020) EZHIP is a specific diagnostic biomarker for posterior fossa ependymomas, group PFA and diffuse midline gliomas H3-WT with EZHIP overexpression. Acta Neuropathol Commun 8:183. https://doi.org/10.1186/s40478-020-01056-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Piunti A, Hashizume R, Morgan MA, Bartom ET, Horbinski CM, Marshall SA, Rendleman EJ, Ma Q, Takahashi YH, Woodfin AR, Misharin AV, Abshiru NA, Lulla RR, Saratsis AM, Kelleher NL, James CD, Shilatifard A (2017) Therapeutic targeting of polycomb and BET bromodomain proteins in diffuse intrinsic pontine gliomas. Nat Med 23:493–500. https://doi.org/10.1038/nm.4296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. 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  PubMed  Google Scholar 

  10. Hassan U, Latif M, Yousaf I, Bin Anees S, Mushtaq S, Akhtar N, Loya A (2021) Morphological Spectrum and Survival Analysis of Diffuse midline glioma with H3K27M mutation. Cureus 13:e17267. https://doi.org/10.7759/cureus.17267

    Article  PubMed  PubMed Central  Google Scholar 

  11. Meyronet D, Esteban-Mader M, Bonnet C, Joly MO, Uro-Coste E, Amiel-Benouaich A, Forest F, Rousselot-Denis C, Burel-Vandenbos F, Bourg V, Guyotat J, Fenouil T, Jouvet A, Honnorat J, Ducray F (2017) Characteristics of H3 K27M-mutant gliomas in adults. Neuro Oncol 19:1127–1134. https://doi.org/10.1093/neuonc/now274

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Park C, Kim TM, Bae JM, Yun H, Kim JW, Choi SH, Lee ST, Lee JH, Park SH, Park CK (2021) Clinical and Genomic Characteristics of Adult Diffuse Midline Glioma. Cancer Res Treat 53:389–398. https://doi.org/10.4143/crt.2020.694

    Article  PubMed  Google Scholar 

  13. Schreck KC, Ranjan S, Skorupan N, Bettegowda C, Eberhart CG, Ames HM, Holdhoff M (2019) Incidence and clinicopathologic features of H3 K27M mutations in adults with radiographically-determined midline gliomas. J Neurooncol 143:87–93. https://doi.org/10.1007/s11060-019-03134-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Schulte JD, Buerki RA, Lapointe S, Molinaro AM, Zhang Y, Villanueva-Meyer JE, Perry A, Phillips JJ, Tihan T, Bollen AW, Pekmezci M, Butowski N, Oberheim Bush NA, Taylor JW, Chang SM, Theodosopoulos P, Aghi MK, Hervey-Jumper SL, Berger MS, Solomon DA, Clarke JL (2020) Clinical, radiologic, and genetic characteristics of histone H3 K27M-mutant diffuse midline gliomas in adults. Neurooncol Adv 2:vdaa142. https://doi.org/10.1093/noajnl/vdaa142

    Article  PubMed  PubMed Central  Google Scholar 

  15. Wang L, Li Z, Zhang M, Piao Y, Chen L, Liang H, Wei Y, Hu Z, Zhao L, Teng L, Lu D (2018) H3 K27M-mutant diffuse midline gliomas in different anatomical locations. Hum Pathol 78:89–96. https://doi.org/10.1016/j.humpath.2018.04.015

    Article  CAS  PubMed  Google Scholar 

  16. Wang Y, Feng LL, Ji PG, Liu JH, Guo SC, Zhai YL, Sankey EW, Wang Y, Xue YR, Wang N, Lou M, Xu M, Chao M, Gao GD, Qu Y, Gong L, Wang L (2020) Clinical features and molecular markers on diffuse midline gliomas with H3K27M mutations: a 43 cases retrospective cohort study. Front Oncol 10:602553. https://doi.org/10.3389/fonc.2020.602553

    Article  PubMed  Google Scholar 

  17. Gallitto M, Lazarev S, Wasserman I, Stafford JM, Wolden SL, Terezakis SA, Bindra RS, Bakst RL (2019) Role of Radiation Therapy in the management of diffuse intrinsic pontine glioma: a systematic review. Adv Radiat Oncol 4:520–531. https://doi.org/10.1016/j.adro.2019.03.009

    Article  PubMed  PubMed Central  Google Scholar 

  18. Abe H, Natsumeda M, Kanemaru Y, Watanabe J, Tsukamoto Y, Okada M, Yoshimura J, Oishi M, Fujii Y (2018) MGMT expression contributes to Temozolomide Resistance in H3K27M-Mutant diffuse midline gliomas and MGMT silencing to Temozolomide Sensitivity in IDH-Mutant Gliomas. Neurol Med Chir (Tokyo) 58:290–295. https://doi.org/10.2176/nmc.ra.2018-0044

    Article  PubMed  Google Scholar 

  19. Cohen KJ, Heideman RL, Zhou T, Holmes EJ, Lavey RS, Bouffet E, Pollack IF (2011) Temozolomide in the treatment of children with newly diagnosed diffuse intrinsic pontine gliomas: a report from the Children’s Oncology Group. Neuro Oncol 13:410–416. https://doi.org/10.1093/neuonc/noq205

    Article  PubMed  PubMed Central  Google Scholar 

  20. Yoon HI, Wee CW, Kim YZ, Seo Y, Im JH, Dho YS, Kim KH, Hong JB, Park JS, Choi SH, Kim MS, Moon J, Hwang K, Park JE, Cho JM, Yoon WS, Kim SH, Kim YI, Kim HS, Sung KS, Song JH, Lee MH, Han MH, Lee SH, Chang JH, Lim DH, Park CK, Lee YS, Gwak HS (2021) The Korean Society for Neuro-Oncology (KSNO) Guideline for adult diffuse midline glioma: Version 2021.1. Brain Tumor Res Treat 9:1–8. https://doi.org/10.14791/btrt.2021.9.e8

    Article  PubMed  PubMed Central  Google Scholar 

  21. Himes BT, Zhang L, Daniels DJ (2019) Treatment strategies in diffuse midline Gliomas with the H3K27M mutation: the role of convection-enhanced delivery in Overcoming Anatomic challenges. Front Oncol 9:31. https://doi.org/10.3389/fonc.2019.00031

    Article  PubMed  PubMed Central  Google Scholar 

  22. Price G, Bouras A, Hambardzumyan D, Hadjipanayis CG (2021) Current knowledge on the immune microenvironment and emerging immunotherapies in diffuse midline glioma. EBioMedicine 69:103453. https://doi.org/10.1016/j.ebiom.2021.103453

    Article  PubMed  PubMed Central  Google Scholar 

  23. Alzoubi H, Maraqa B, Hasasna N, Giangaspero F, Antonelli M, Gianno F, Arcella A, Al-Hussaini M (2021) Diffuse midline glioma H3 K27M-mutant in adults: a report of six cases and literature review. Clin Neuropathol 40:108–117. https://doi.org/10.5414/np301331

    Article  PubMed  Google Scholar 

  24. Bhattarai AM, Mainali G, Jha P, Karki P, Adhikari A, Pandit A, Bhattarai AM (2022) Diffuse midline glioma H3K27M mutation in adult: a case report. Ann Med Surg (Lond) 76:103567. https://doi.org/10.1016/j.amsu.2022.103567

    Article  PubMed  Google Scholar 

  25. Fleischhack G, Massimino M, Warmuth-Metz M, Khuhlaeva E, Janssen G, Graf N, Rutkowski S, Beilken A, Schmid I, Biassoni V, Gorelishev SK, Kramm C, Reinhard H, Schlegel PG, Kortmann RD, Reuter D, Bach F, Iznaga-Escobar NE, Bode U (2019) Nimotuzumab and radiotherapy for treatment of newly diagnosed diffuse intrinsic pontine glioma (DIPG): a phase III clinical study. J Neurooncol 143:107–113. https://doi.org/10.1007/s11060-019-03140-z

    Article  CAS  PubMed  Google Scholar 

  26. Zaghloul MS, Nasr A, Tolba M, Refaat A, Youssef A, Mosaab A, Enayet A, Arafa O, Maher E, Eldebawy E (2022) Hypofractionated Radiation Therapy for diffuse intrinsic pontine glioma: a Noninferiority Randomized Study including 253 children. Int J Radiat Oncol Biol Phys 113:360–368. https://doi.org/10.1016/j.ijrobp.2022.01.054

    Article  PubMed  Google Scholar 

  27. Amsbaugh MJ, Mahajan A, Thall PF, McAleer MF, Paulino AC, Grosshans D, Khatua S, Ketonen L, Fontanilla H, McGovern SL (2019) A phase 1/2 trial of reirradiation for diffuse intrinsic pontine glioma. Int J Radiat Oncol Biol Phys 104:144–148. https://doi.org/10.1016/j.ijrobp.2018.12.043

    Article  PubMed  Google Scholar 

  28. Janssens GO, Gandola L, Bolle S, Mandeville H, Ramos-Albiac M, van Beek K, Benghiat H, Hoeben B, Morales La Madrid A, Kortmann RD, Hargrave D, Menten J, Pecori E, Biassoni V, von Bueren AO, van Vuurden DG, Massimino M, Sturm D, Peters M, Kramm CM (2017) Survival benefit for patients with diffuse intrinsic pontine glioma (DIPG) undergoing re-irradiation at first progression: a matched-cohort analysis on behalf of the SIOP-E-HGG/DIPG working group. Eur J Cancer 73:38–47. https://doi.org/10.1016/j.ejca.2016.12.007

    Article  PubMed  Google Scholar 

  29. Massimino M, Biassoni V, Miceli R, Schiavello E, Warmuth-Metz M, Modena P, Casanova M, Pecori E, Giangaspero F, Antonelli M, Buttarelli FR, Potepan P, Pollo B, Nunziata R, Spreafico F, Podda M, Anichini A, Clerici CA, Sardi I, De Cecco L, Bode U, Bach F, Gandola L (2014) Results of nimotuzumab and vinorelbine, radiation and re-irradiation for diffuse pontine glioma in childhood. J Neurooncol 118:305–312. https://doi.org/10.1007/s11060-014-1428-z

    Article  CAS  PubMed  Google Scholar 

  30. Chen CCL, Deshmukh S, Jessa S, Hadjadj D, Lisi V, Andrade AF, Faury D, Jawhar W, Dali R, Suzuki H, Pathania M, Dubois AD, Woodward F, Hébert E, Coutelier S, Karamchandani M, Albrecht J, Brandner S, De Jay S, Gayden N, Bajic T, Harutyunyan A, Marchione AS, Mikael DM, Juretic LG, Zeinieh N, Russo M, Maestro C, Bassenden N, Hauser AV, Virga P, Bognar J, Klekner L, Zapotocky A, Vicha M, Krskova A, Vanova L, Zamecnik K, Sumerauer J, Ekert D, Ziegler PG, Ellezam DS, Filbin B, Blanchette MG, Hansford M, Khuong-Quang JR, Berghuis DA, Weil AM, Garcia AG, Garzia BA, Mack L, Beroukhim SC, Ligon R, Taylor KL, Bandopadhayay MD, Kramm P, Pfister C, Korshunov SM, Sturm A, Jones D, Salomoni DTW, Kleinman P, Jabado CL N (2020) Histone H3.3G34-Mutant Interneuron progenitors co-opt PDGFRA for Gliomagenesis. Cell 183:1617–1633e1622. https://doi.org/10.1016/j.cell.2020.11.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Tan JY, Wijesinghe IVS, Alfarizal Kamarudin MN, Parhar I (2021) Paediatric gliomas: BRAF and histone H3 as biomarkers, therapy and perspective of Liquid biopsies. Cancers (Basel) 13. https://doi.org/10.3390/cancers13040607

  32. Vanan MI, Underhill DA, Eisenstat DD (2017) Targeting epigenetic pathways in the treatment of Pediatric diffuse (high Grade) Gliomas. Neurotherapeutics 14:274–283. https://doi.org/10.1007/s13311-017-0514-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Zanazzi G, Liechty BL, Pendrick D, Krasnozhen-Ratush O, Snuderl M, Allen JC, Garvin JH, Mansukhani MM, Roth KA, Hsiao SJ (2020) Diffuse midline glioma with novel, potentially targetable, FGFR2-VPS35 fusion. Cold Spring Harb Mol Case Stud 6. https://doi.org/10.1101/mcs.a005660

  34. Roberts HJ, Ji S, Picca A, Sanson M, Garcia M, Snuderl M, Schüller U, Picart T, Ducray F, Green AL, Nakano Y, Sturm D, Abdullaev Z, Aldape K, Dang D, Kumar-Sinha C, Wu YM, Robinson D, Vo JN, Chinnaiyan AM, Cartaxo R, Upadhyaya SA, Mody R, Chiang J, Baker S, Solomon D, Venneti S, Pratt D, Waszak SM, Koschmann C (2023) Clinical, genomic, and epigenomic analyses of H3K27M-mutant diffuse midline glioma long-term survivors reveal a distinct group of tumors with MAPK pathway alterations. Acta Neuropathol 146:849–852. https://doi.org/10.1007/s00401-023-02640-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. van den Bent MJ, Tesileanu CMS, Wick W, Sanson M, Brandes AA, Clement PM, Erridge S, Vogelbaum MA, Nowak AK, Baurain JF, Mason WP, Wheeler H, Chinot OL, Gill S, Griffin M, Rogers L, Taal W, Rudà R, Weller M, McBain C, Reijneveld J, Enting RH, Caparrotti F, Lesimple T, Clenton S, Gijtenbeek A, Lim E, Herrlinger U, Hau P, Dhermain F, de Heer I, Aldape K, Jenkins RB, Dubbink HJ, Kros JM, Wesseling P, Nuyens S, Golfinopoulos V, Gorlia T, French P, Baumert BG (2021) Adjuvant and concurrent temozolomide for 1p/19q non-co-deleted anaplastic glioma (CATNON; EORTC study 26053 – 22054): second interim analysis of a randomised, open-label, phase 3 study. Lancet Oncol 22:813–823. https://doi.org/10.1016/s1470-2045(21)00090-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. van den Bent M, Saratsis AM, Geurts M, Franceschi E (2023) H3 K27M-altered glioma and diffuse intrinsic pontine Glioma: semi-systematic review of Treatment Landscape and future directions. Neuro Oncol. https://doi.org/10.1093/neuonc/noad220

    Article  PubMed  PubMed Central  Google Scholar 

  37. Chi AS, Tarapore RS, Hall MD, Shonka N, Gardner S, Umemura Y, Sumrall A, Khatib Z, Mueller S, Kline C, Zaky W, Khatua S, Weathers SP, Odia Y, Niazi TN, Daghistani D, Cherrick I, Korones D, Karajannis MA, Kong XT, Minturn J, Waanders A, Arillaga-Romany I, Batchelor T, Wen PY, Merdinger K, Schalop L, Stogniew M, Allen JE, Oster W, Mehta MP (2019) Pediatric and adult H3 K27M-mutant diffuse midline glioma treated with the selective DRD2 antagonist ONC201. J Neurooncol 145:97–105. https://doi.org/10.1007/s11060-019-03271-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Gardner SL, Tarapore RS, Allen J, McGovern SL, Zaky W, Odia Y, Daghistani D, Diaz Z, Hall MD, Khatib Z, Koschmann C, Cantor E, Kurokawa R, MacDonald TJ, Aguilera D, Vitanza NA, Mueller S, Kline C, Lu G, Allen JE, Khatua S (2022) Phase I dose escalation and expansion trial of single agent ONC201 in pediatric diffuse midline gliomas following radiotherapy. Neurooncol Adv 4:vdac143. https://doi.org/10.1093/noajnl/vdac143

    Article  PubMed  PubMed Central  Google Scholar 

  39. Jackson ER, Duchatel RJ, Staudt DE, Persson ML, Mannan A, Yadavilli S, Parackal S, Game S, Chong WC, Jayasekara WSN, Grand ML, Kearney PS, Douglas AM, Findlay IJ, Germon ZP, McEwen HP, Beitaki TS, Patabendige A, Skerrett-Byrne DA, Nixon B, Smith ND, Day B, Manoharan N, Nagabushan S, Hansford JR, Govender D, McCowage GB, Firestein R, Howlett M, Endersby R, Gottardo NG, Alvaro F, Waszak SM, Larsen MR, Colino-Sanguino Y, Valdes-Mora F, Rakotomalala A, Meignan S, Pasquier E, André N, Hulleman E, Eisenstat DD, Vitanza NA, Nazarian J, Koschmann C, Mueller S, Cain JE, Dun MD (2023) ONC201 in Combination with Paxalisib for the Treatment of H3K27-Altered Diffuse Midline Glioma. Cancer Res Of1–of17. https://doi.org/10.1158/0008-5472.Can-23-0186

  40. Purow B (2022) ONC201 and ONC206: metabolically ClipPing the wings of diffuse midline glioma. Neuro Oncol 24:1452–1453. https://doi.org/10.1093/neuonc/noac103

    Article  PubMed  PubMed Central  Google Scholar 

  41. Tucker K, Yin Y, Staley SA, Zhao Z, Fang Z, Fan Y, Zhang X, Suo H, Sun W, Prabhu VV, Allen JE, Zhou C, Bae-Jump VL (2022) ONC206 has anti-tumorigenic effects in human ovarian cancer cells and in a transgenic mouse model of high-grade serous ovarian cancer. Am J Cancer Res 12:521–536

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

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Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Author information

Authors and Affiliations

  1. Nervous System Medical Oncology Department, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bellaria Hospital, Bologna, 40139, Italy

    Vincenzo Di Nunno, Alicia Tosoni & Enrico Franceschi

  2. Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy

    Giuseppe Lombardi, Martina Corrà, Marta Padovan, Marta Maccari & Mario Caccese

  3. Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milano, Italy

    Matteo Simonelli

  4. IRCCS Humanitas Research Hospital, Rozzano, Milano, Italy

    Matteo Simonelli, Antonio Di Muzio & Angelo Dipasquale

  5. Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University, Policlinico Umberto I, Rome, Italy

    Giuseppe Minniti & Manila Antonelli

  6. IRCCS Istituto Neurologico Mediterraneo Neuromed, Pozzilli, Italy

    Giuseppe Minniti

  7. Onco-Hematology, Cell Therapy, Gene Therapies and Hemopoietic Transplant, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy

    Angela Mastronuzzi & Valentina Di Ruscio

  8. Neuro-Oncology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy

    Giorgia Simonetti & Antonio Silvani

  9. Unit of Immunotherapy of Brain Tumors, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, 20133, Italy

    Arianna Berlendis

  10. Unit of Neuroepidemiology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, Milan, 20133, Italy

    Mariangela Farinotti

  11. Unit of Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, Milan, 20133, Italy

    Bianca Pollo

  12. IRCCS-Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy

    Sofia Asioli

  13. Department of Biomedical and Neuromotor Sciences (DIBINEM)-Surgical Pathology Section, Alma Mater Studiorum - University of Bologna, Bologna, Italy

    Sofia Asioli

  14. Department of Pharmacy and Biotechnology (FaBit), University of Bologna, Bologna, Italy

    Dario De Biase

  15. Solid Tumor Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

    Dario De Biase

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  1. Vincenzo Di Nunno
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  2. Giuseppe Lombardi
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Contributions

Conceptualization: VDN, EF, and AT contributed to conceptualization. Data Curation: VDN performed formal analysis and data curation. The Investigation was carried out by all authors. VDN, GL, AS, MS, GM, AM, VDR, MC, MP, MP, MM, MC, GS, AB, MF, BP, MA, ADM, SA, DDB, AT, AD, EF reviewed methodology VDN, EF written the first version. All authors reviewed and edited this paper. All authors read and approved the final version of this manuscript. Vincenzo Di Nunno and Giuseppe Lombardi are co-first authors of the present manuscript. Antonio Silvani and Enrico Franceschi are co-last authors of the present manuscript.

Corresponding author

Correspondence to Enrico Franceschi.

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Competing interests

The authors declare no competing interests.

Ethics approval

The study was approved by the Ethical Committee of Azienda Sanitaria Locale di Bologna (protocol number CE09113, Bologna, Italy). All information regarding the human material was managed using anonymous numerical codes, and all samples were handled in compliance with the Helsinki Declaration.

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Vincenzo Di Nunno and Giuseppe Lombardi are Co-primary Authors.

Antonio Silvani and Enrico Franceschi are Co-last Authors.

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Di Nunno, V., Lombardi, G., Simonelli, M. et al. The role of adjuvant chemotherapy in patients with H3K27 altered diffuse midline gliomas: a multicentric retrospective study. J Neurooncol 167, 145–154 (2024). https://doi.org/10.1007/s11060-024-04589-3

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  • DOI: https://doi.org/10.1007/s11060-024-04589-3

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