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Chemoradiation for anaplastic oligodendrogliomas: clinical outcomes and prognostic value of molecular markers

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Abstract

Combination of procarbazine, lomustine and vincristine (PCV) with radiation therapy (RT) has been associated with longer survival in patients with anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA), especially in those with chromosome 1p/19q codeletion. We report a multicenter retrospective study of 84 consecutive adult patients with AO and AOA treated with RT plus concomitant and adjuvant temozolomide (TMZ) between February 2004 and January 2011. Correlations between chromosome 1p/19q codeletion, isocitrate dehydrogenase1 (IDH1) mutation, and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation with survival outcomes have been analyzed. For all 84 patients the median overall survival (OS) and progression-free survival rates were 55.6 and 45.2 months, respectively. Grade 3 or 4 hematological toxicity occurred in 17 % of patients. Chromosome 1p/19q codeletion was detected in 57 %, IDH1 mutation in 63 %, and MGMT promoter methylation in 74 % of evaluable patients. In multivariate analysis the presence of chromosome 1p/19q codeletion was associated with significant survival benefit (median OS 34 months in noncodeleted tumors and not reached in codeleted tumors; HR 0.16, 95 % CI 0.03–0.45; P = 0.005). IDH1 mutation was also of prognostic significance for longer survival (P = 0.001; HR 0.20, 95 % 0.06–0.41), whereas MGMT promoter methylation was only of borderline significance. The study indicates that RT with concomitant and adjuvant TMZ is a relatively safe treatment associated with longer survival in patients with 1p/19q codeleted and IDH1 mutated tumors. Results from ongoing randomized studies will be essential to clarify if RT plus TMZ may provide survival as good as or better than RT combined with PCV for patients with AO and AOA.

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References

  1. Dolecek TA, Propp JM, Stroup NE, Kruchko C (2012) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005–2009. Neuro Oncol 14(Suppl 5):v1–v49

    Article  PubMed Central  PubMed  Google Scholar 

  2. Van den Bent MJ, Kros JM, Heimans JJ, Pronk LC, van Groeningen CJ, Krouwer HG, Taphoorn MJ, Zonnenberg BA, Tijssen CC, Twijnstra A, Punt CJ, Boogerd W (1998) Response rate and prognostic factors of recurrent oligodendroglioma treated with procarbazine, CCNU, and vincristine chemotherapy. Dutch Neuro-oncology Group. Neurology 51:1140–1145

    Article  PubMed  Google Scholar 

  3. Paleologos NA, Macdonald DR, Vick NA, Cairncross JG (1999) Neoadjuvant procarbazine, CCNU, and vincristine for anaplastic and aggressive oligodendroglioma. Neurology 53:1141–1143

    Article  CAS  PubMed  Google Scholar 

  4. Smith JS, Perry A, Borell TJ, Lee HK, O’Fallon J, Hosek SM, Kimmel D, Yates A, Burger PC, Scheithauer BW, Jenkins RB (2000) Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas. J Clin Oncol 18:636–645

    CAS  PubMed  Google Scholar 

  5. Brandes AA, Tosoni A, Vastola F, Pasetto LM, Coria B, Danieli D, Iuzzolino P, Gardiman M, Talacchi A, Ermani M (2004) Efficacy and feasibility of standard procarbazine, lomustine, and vincristine chemotherapy in anaplastic oligodendroglioma and oligoastrocytoma recurrent after radiotherapy. A phase II study. Cancer 101:2079–2085

    Article  CAS  PubMed  Google Scholar 

  6. Van den Bent MJ, Brandes AA, Taphoorn MJ, Kros JM, Kouwenhoven MC, Delattre JY, Bernsen HJ, Frenay M, Tijssen CC, Grisold W, Sipos L, Enting RH, French PJ, Dinjens WN, Vecht CJ, Allgeier A, Lacombe D, Gorlia T, Hoang-Xuan K (2013) Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol 31:344–350

    Article  PubMed  Google Scholar 

  7. Cairncross G, Wang M, Shaw E, Jenkins R, Brachman D, Buckner J, Fink K, Souhami L, Laperriere N, Curran W, Mehta M (2013) Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol 31:337–343

    Article  CAS  PubMed  Google Scholar 

  8. Van den Bent MJ, Carpentier AF, Brandes AA, Sanson M, Taphoorn MJ, Bernsen HJ, Frenay M, Tijssen CC, Grisold W, Sipos L, Haaxma-Reiche H, Kros JM, van Kouwenhoven MC, Vecht CJ, Allgeier A, Lacombe D, Gorlia T (2006) Adjuvant procarbazine, lomustine, and vincristine improves progression-free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas and oligoastrocytomas: a randomized European Organisation for Research and Treatment of Cancer phase III trial. J Clin Oncol 24:2715–2722

    Article  PubMed  Google Scholar 

  9. Intergroup Radiation Therapy Oncology Group Trial 9402, Cairncross G, Berkey B, Shaw E, Jenkins R, Scheithauer B, Brachman D, Buckner J, Fink K, Souhami L, Laperierre N, Mehta M, Curran W (2006) Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402. J Clin Oncol 24:2707–2714

    Article  CAS  PubMed  Google Scholar 

  10. Van den Bent MJ, Chinot O, Boogerd W, Bravo Marques J, Taphoorn MJ, Kros JM, van der Rijt CC, Vecht CJ, De Beule N, Baron B (2003) Second-line chemotherapy with temozolomide in recurrent oligodendroglioma after PCV (procarbazine, lomustine and vincristine) chemotherapy: EORTC Brain Tumor Group phase II study 26972. Ann Oncol 14:599–602

    Article  PubMed  Google Scholar 

  11. Van den Bent MJ, Taphoorn MJ, Brandes AA, Menten J, Stupp R, Frenay M, Chinot O, Kros JM, van der Rijt CC, Vecht ChJ, Allgeier A, Gorlia T, European Organization for Research and Treatment of Cancer Brain Tumor Group (2003) Phase II study of first-line chemotherapy with temozolomide in recurrent oligodendroglial tumors: the European Organization for Research and Treatment of Cancer Brain Tumor Group Study 26971. J Clin Oncol 21:2525–2528

    Article  PubMed  Google Scholar 

  12. Taliansky-Aronov A, Bokstein F, Lavon I, Siegal T (2006) Temozolomide treatment for newly diagnosed anaplastic oligodendrogliomas: a clinical efficacy trial. J Neurooncol 79:153–157

    Article  CAS  PubMed  Google Scholar 

  13. Mikkelsen T, Doyle T, Anderson J, Margolis J, Paleologos N, Gutierrez J, Croteau D, Hasselbach L, Avedissian R, Schultz L (2009) Temozolomide single-agent chemotherapy for newly diagnosed anaplastic oligodendroglioma. J Neurooncol 92:57–63

    Article  CAS  PubMed  Google Scholar 

  14. Wick W, Hartmann C, Engel C, Stoffels M, Felsberg J, Stockhammer F, Sabel MC, Koeppen S, Ketter R, Meyermann R, Rapp M, Meisner C, Kortmann RD, Pietsch T, Wiestler OD, Ernemann U, Bamberg M, Reifenberger G, von Deimling A, Weller M (2009) NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol 27:5874–5880 Erratum in: J Clin Oncol 2010 28:708

    Article  CAS  PubMed  Google Scholar 

  15. Gan HK, Rosenthal MA, Dowling A, Kalnins R, Algar E, Wong N, Benson A, Woods AM, Cher L (2010) A phase II trial of primary temozolomide in patients with grade III oligodendroglial brain tumors. Neuro Oncol 12:500–507

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Ducray F, del Rio MS, Carpentier C, Psimaras D, Idbaih A, Dehais C, Kaloshi G, Mokhtari K, Taillibert S, Laigle-Donadey F, Omuro A, Sanson M, Delattre JY, Hoang-Xuan K (2011) Up-front temozolomide in elderly patients with anaplastic oligodendroglioma and oligoastrocytoma. J Neurooncol 101:457–462

    Article  CAS  PubMed  Google Scholar 

  17. Bauman GS, Ino Y, Ueki K, Zlatescu MC, Fisher BJ, Macdonald DR, Stitt L, Louis DN, Cairncross JG (2000) Allelic loss of chromosome 1p and radiotherapy plus chemotherapy in patients with oligodendrogliomas. Int J Radiat Oncol Biol Phys 48:825–830

    Article  CAS  PubMed  Google Scholar 

  18. Chahlavi A, Kanner A, Peereboom D, Staugaitis SM, Elson P, Barnett G (2003) Impact of chromosome 1p status in response of oligodendroglioma to temozolomide: preliminary results. J Neurooncol 61:267–273

    Article  PubMed  Google Scholar 

  19. Thiessen B, Maguire JA, McNeil K, Huntsman D, Martin MA, Horsman D (2003) Loss of heterozygosity for loci on chromosome arms 1p and 10q in oligodendroglial tumors: relationship to outcome and chemosensitivity. J Neurooncol 64:271–278

    Article  PubMed  Google Scholar 

  20. Jiang H, Ren X, Cui X, Wang J, Jia W, Zhou Z, Lin S (2013) 1p/19q codeletion and IDH1/2 mutation identified a subtype of anaplastic oligoastrocytomas with prognosis as favorable as anaplastic oligodendrogliomas. Neuro Oncol 15:775–782

    Article  CAS  PubMed  Google Scholar 

  21. Frenel JS, Leux C, Loussouarn D, Le Loupp AG, Leclair F, Aumont M, Mervoyer A, Martin S, Denis MG, Campone M (2013) Combining two biomarkers, IDH1/2 mutations and 1p/19q codeletion, to stratify anaplastic oligodendroglioma in three groups: a single-center experience. J Neurooncol 114(1):85–91

    Article  CAS  PubMed  Google Scholar 

  22. Brell M, Tortosa A, Verger E, Gil JM, Viñolas N, Villá S, Acebes JJ, Caral L, Pujol T, Ferrer I, Ribalta T, Graus F (2005) Prognostic significance of O6-methylguanine-DNA methyltransferase determined by promoter hypermethylation and immunohistochemical expression in anaplastic gliomas. Clin Cancer Res 11:5167–5174

    Article  CAS  PubMed  Google Scholar 

  23. Quinn JA, Reardon DA, Friedman AH, Rich JN, Sampson JH, Provenzale JM, McLendon RE, Gururangan S, Bigner DD, Herndon JE 2nd, Avgeropoulos N, Finlay J, Tourt-Uhlig S, Affronti ML, Evans B, Stafford-Fox V, Zaknoen S, Friedman HS (2003) Phase II trial of temozolomide in patients with progressive low-grade glioma. J Clin Oncol 21:646–651

    Article  CAS  PubMed  Google Scholar 

  24. Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, Degroot J, Wick W, Gilbert MR, Lassman AB, Tsien C, Mikkelsen T, Wong ET, Chamberlain MC, Stupp R, Lamborn KR, Vogelbaum MA, van den Bent MJ, Chang SM (2010) Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 28:1963–1972

    Article  PubMed  Google Scholar 

  25. Minniti G, Salvati M, Arcella A, Buttarelli F, D’Elia A, Lanzetta G, Esposito V, Scarpino S, Maurizi Enrici R, Giangaspero F (2011) Correlation between O6-methylguanine-DNA methyltransferase and survival in elderly patients with glioblastoma treated with radiotherapy plus concomitant and adjuvant temozolomide. J Neurooncol 102:311–316

    Article  CAS  PubMed  Google Scholar 

  26. Vogelbaum MA, Berkey B, Peereboom D, Macdonald D, Giannini C, Suh JH, Jenkins R, Herman J, Brown P, Blumenthal DT, Biggs C, Schultz C, Mehta M (2009) Phase II trial of preirradiation and concurrent temozolomide in patients with newly diagnosed anaplastic oligodendrogliomas and mixed anaplastic oligoastrocytomas: RTOG BR0131. Neuro Oncol 11:167–175

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Abrey LE, Louis DN, Paleologos N, Lassman AB, Raizer JJ, Mason W, Finlay J, MacDonald DR, DeAngelis LM, Cairncross JG, Oligodendroglioma Study Group (2007) Survey of treatment recommendations for anaplastic oligodendroglioma. Neuro Oncol 9:314–318

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Panageas KS, Iwamoto FM, Cloughesy TF, Aldape KD, Rivera AL, Eichler AF, Louis DN, Paleologos NA, Fisher BJ, Ashby LS, Cairncross JG, Roldán Urgoiti GB, Wen PY, Ligon KL, Schiff D, Robins HI, Rocque BG, Chamberlain MC, Mason WP, Weaver SA, Green RM, Kamar FG, Abrey LE, Deangelis LM, Jhanwar SC, Rosenblum MK, Lassman AB (2012) Initial treatment patterns over time for anaplastic oligodendroglial tumors. Neuro Oncol 14:761–767

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

We thank Professor Alessandro Bozzao, dr Andrea Romano and dr Guido Trasimeni neuroradiologists, Neuroradiology Unit, Sant’Andrea Hospital, for reviewing all MRI scans.

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The authors declare that they have no conflict of interest.

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Correspondence to Giuseppe Minniti.

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Minniti, G., Arcella, A., Scaringi, C. et al. Chemoradiation for anaplastic oligodendrogliomas: clinical outcomes and prognostic value of molecular markers. J Neurooncol 116, 275–282 (2014). https://doi.org/10.1007/s11060-013-1288-y

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  • DOI: https://doi.org/10.1007/s11060-013-1288-y

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