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Management of patients with recurrence of diffuse low grade glioma

A systematic review and evidence-based clinical practice guideline

  • Topic Review & Clinical Guidelines
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Target population

These recommendations apply to adult patients with recurrent low-grade glioma (LGG) with initial pathologic diagnosis of a WHO grade II infiltrative glioma (oligodendroglioma, astrocytoma, or oligo-astrocytoma).

Pathology at recurrence

Question

Do pathologic and molecular characteristics predict outcome/malignant transformation at recurrence?

Recommendations

IDH status and recurrence

(Level III) IDH mutation status should be determined as LGGs with IDH mutations have a shortened time to recurrence. It is unclear whether knowledge of IDH mutation status provides benefit in predicting time to progression or overall survival.

TP53 status and recurrence

(Level III) TP53 mutations occur early in LGG pathogenesis, remain stable, and are not recommended as a marker of predisposition to malignant transformation at recurrence or other measures of prognosis.

MGMT status and recurrence

(Level III) Assessment of MGMT status is recommended as an adjunct to assessing prognosis as LGGs with MGMT promoter methylation are associated with shorter PFS (in the absence of TMZ) and longer post-recurrence survival (in the presence of TMZ), ultimately producing similar overall survival to LGGs without MGMT methylationThe available retrospective reports are conflicting and comparisons between reports are limited

CDK2NA status and recurrence

(Level III) Assessment of CDK2NA status is recommended when possible as the loss of expression of the CDK2NA via either methylation or loss of chromosome 9p is associated with malignant progression of LGGs.

Proliferative index and recurrence

(Level III) It is recommended that proliferative indices (MIB-1 or BUdR) be measured in LGGs as higher proliferation indices are associated with increased likelihood of recurrence and shorter progression free and overall survival.

1p/19q status and recurrence

There is insufficient evidence to make any recommendations.

Chemotherapy at recurrence

Question

What role does chemotherapy have in LGG recurrence?

Recommendations

Temozolomide and recurrence

(Level III) Temozolomide is recommended in the therapy of recurrent LGG as it may improve clinical symptoms. Oligodendrogliomas and tumors with 1p/19q co-deletion may derive the most benefit.

PCV and recurrence

(Level III) PCV is recommended in the therapy of LGG at recurrence as it may improve clinical symptoms with the strongest evidence being for oligodendrogliomas.

Carboplatin and recurrence

(Level III) Carboplatin is not recommended as there is no significant benefit from carboplatin as single agent therapy for recurrent LGGs.

Other treatments (Nitrosureas, Hydroxyurea/Imanitib, irinotecan, paclitaxel) and recurrence

There is insufficient evidence to make any recommendations. It is recommended that individuals with recurrent LGGs be enrolled in a properly designed clinical trial to assess these chemotherapeutic agents.

Radiation at recurrence

Question

What role does radiation have in LGG recurrence?

Recommendations

Radiation at recurrence with no previous irradiation

(Level III) Radiation is recommended at recurrence if there was no previous radiation treatment.

Re-irradiation at recurrence

(Level III) It is recommended that re-irradiation be considered in the setting of LGG recurrence as it may provide benefit in disease control.

Surgery at recurrence

There is insufficient evidence to make any specific recommendations. It is recommended that individuals with recurrent LGGs be enrolled in a properly designed clinical trial to assess the role of surgery at recurrence.

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References

  1. Juratli TA, Kirsch M, Robel K et al (2012) IDH mutations as an early and consistent marker in low-grade astrocytomas WHO grade II and their consecutive secondary high-grade gliomas. J Neurooncol 108(3):403–410

    Article  CAS  PubMed  Google Scholar 

  2. Hartmann C, Hentschel B, Tatagiba M et al (2011) Molecular markers in low-grade gliomas: predictive or prognostic? Clin Cancer Res 17(13):4588–4599

    Article  CAS  PubMed  Google Scholar 

  3. Thon N, Eigenbrod S, Kreth S et al (2012) IDH1 mutations in grade II astrocytomas are associated with unfavorable progression-free survival and prolonged postrecurrence survival. Cancer 118(2):452–460

    Article  CAS  PubMed  Google Scholar 

  4. Ishii N, Tada M, Hamou MF et al (1999) Cells with TP53 mutations in low grade astrocytic tumors evolve clonally to malignancy and are an unfavorable prognostic factor. Oncogene 18(43):5870–5878

    Article  CAS  PubMed  Google Scholar 

  5. Watanabe K, Sato K, Biernat W et al (1997) Incidence and timing of p53 mutations during astrocytoma progression in patients with multiple biopsies. Clin Cancer Res 3(4):523–530

    CAS  PubMed  Google Scholar 

  6. Kraus JA, Bolln C, Wolf HK et al (1994) TP53 alterations and clinical outcome in low grade astrocytomas. Genes Chromosomes Cancer 10(2):143–149

    Article  CAS  PubMed  Google Scholar 

  7. Groenendijk FH, Taal W, Dubbink HJ et al (2011) MGMT promoter hypermethylation is a frequent, early, and consistent event in astrocytoma progression, and not correlated with TP53 mutation. J Neurooncol 101(3):405–417

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Heesters MA, Koudstaal J, Go KG, Molenaar WM (2002) Proliferation and apoptosis in long-term surviving low grade gliomas in relation to radiotherapy. J Neurooncol 58(2):157–165

    Article  PubMed  Google Scholar 

  9. Reifenberger J, Ring GU, Gies U et al (1996) Analysis of p53 mutation and epidermal growth factor receptor amplification in recurrent gliomas with malignant progression. J Neuropathol Exp Neurol 55(7):822–831

    Article  CAS  PubMed  Google Scholar 

  10. Watanabe T, Katayama Y, Yoshino A et al (2007) Aberrant hypermethylation of p14ARF and O6-methylguanine-DNA methyltransferase genes in astrocytoma progression. Brain Pathol 17(1):5–10

    Article  CAS  PubMed  Google Scholar 

  11. Laffaire J, Everhard S, Idbaih A et al (2011) Methylation profiling identifies 2 groups of gliomas according to their tumorigenesis. Neuro Oncol 13(1):84–98

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Idbaih A, Carvalho Silva R, Criniere E et al (2008) Genomic changes in progression of low-grade gliomas. J Neurooncol 90(2):133–140

    Article  CAS  PubMed  Google Scholar 

  13. Hoshi M, Yoshida K, Shimazaki K, Sasaki H, Otani M, Kawase T (1997) Correlation between MIB-1 staining indices and recurrence in low-grade astrocytomas. Brain Tumor Pathol 14(1):47–51

    Article  CAS  PubMed  Google Scholar 

  14. Ito S, Chandler KL, Prados MD et al (1994) Proliferative potential and prognostic evaluation of low-grade astrocytomas. J Neurooncol 19(1):1–9

    Article  CAS  PubMed  Google Scholar 

  15. Jung TY, Jung S, Moon JH, Kim IY, Moon KS, Jang WY (2011) Early prognostic factors related to progression and malignant transformation of low-grade gliomas. Clin Neurol Neurosurg 113(9):752–757

    Article  PubMed  Google Scholar 

  16. Jaeckle KA, Decker PA, Ballman KV et al (2011) Transformation of low grade glioma and correlation with outcome: an NCCTG database analysis. J Neurooncol 104(1):253–259

    Article  CAS  PubMed  Google Scholar 

  17. Chaichana KL, McGirt MJ, Laterra J, Olivi A, Quinones-Hinojosa A (2010) Recurrence and malignant degeneration after resection of adult hemispheric low-grade gliomas. J Neurosurg 112(1):10–17

    Article  PubMed  Google Scholar 

  18. Taal W, Dubbink HJ, Zonnenberg CB et al (2011) First-line temozolomide chemotherapy in progressive low-grade astrocytomas after radiotherapy: molecular characteristics in relation to response. Neuro Oncol 13(2):235–241

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Kesari S, Schiff D, Drappatz J et al (2009) Phase II study of protracted daily temozolomide for low-grade gliomas in adults. Clin Cancer Res 15(1):330–337

    Article  CAS  PubMed  Google Scholar 

  20. Tosoni A, Franceschi E, Ermani M et al (2008) Temozolomide three weeks on and one week off as first line therapy for patients with recurrent or progressive low grade gliomas. J Neurooncol 89(2):179–185

    Article  CAS  PubMed  Google Scholar 

  21. Kaloshi G, Benouaich-Amiel A, Diakite F et al (2007) Temozolomide for low-grade gliomas: predictive impact of 1p/19q loss on response and outcome. Neurology 68(21):1831–1836

    Article  CAS  PubMed  Google Scholar 

  22. Levin N, Lavon I, Zelikovitsh B et al (2006) Progressive low-grade oligodendrogliomas: response to temozolomide and correlation between genetic profile and O6-methylguanine DNA methyltransferase protein expression. Cancer 106(8):1759–1765

    Article  CAS  PubMed  Google Scholar 

  23. Everaert E, Neyns B, Joosens E, Strauven T, Branle F, Menten J (2004) Temozolomide for the treatment of recurrent supratentorial glioma: results of a compassionate use program in Belgium. J Neurooncol 70(1):37–48

    Article  PubMed  Google Scholar 

  24. Pace A, Vidiri A, Galie E et al (2003) Temozolomide chemotherapy for progressive low-grade glioma: clinical benefits and radiological response. Ann Oncol 14(12):1722–1726

    Article  CAS  PubMed  Google Scholar 

  25. Quinn JA, Reardon DA, Friedman AH et al (2003) Phase II trial of temozolomide in patients with progressive low-grade glioma. J Clin Oncol 21(4):646–651

    Article  CAS  PubMed  Google Scholar 

  26. van den Bent MJ, Taphoorn MJ, Brandes AA et al (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(13):2525–2528

    Article  PubMed  Google Scholar 

  27. van den Bent MJ, Chinot O, Boogerd W et al (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(4):599–602

    Article  PubMed  Google Scholar 

  28. Kouwenhoven MC, Kros JM, French PJ et al (2006) 1p/19q loss within oligodendroglioma is predictive for response to first line temozolomide but not to salvage treatment. Eur J Cancer 42(15):2499–2503

    Article  CAS  PubMed  Google Scholar 

  29. 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(3):267–273

    Article  PubMed  Google Scholar 

  30. Dubbink HJ, Taal W, van Marion R et al (2009) IDH1 mutations in low-grade astrocytomas predict survival but not response to temozolomide. Neurology 73(21):1792–1795

    Article  CAS  PubMed  Google Scholar 

  31. Hoang-Xuan K, Capelle L, Kujas M et al (2004) Temozolomide as initial treatment for adults with low-grade oligodendrogliomas or oligoastrocytomas and correlation with chromosome 1p deletions. J Clin Oncol 22(15):3133–3138

    Article  CAS  PubMed  Google Scholar 

  32. Soffietti R, Ruda R, Bradac GB, Schiffer D (1998) PCV chemotherapy for recurrent oligodendrogliomas and oligoastrocytomas. Neurosurgery 43(5):1066–1073

    Article  CAS  PubMed  Google Scholar 

  33. van den Bent MJ, Kros JM, Heimans JJ et al (1998) Response rate and prognostic factors of recurrent oligodendroglioma treated with procarbazine, CCNU, and vincristine chemotherapy. Dutch neuro-oncology group. Neurology 51(4):1140–1145

    Article  PubMed  Google Scholar 

  34. Friedman HS, Krischer JP, Burger P et al (1992) Treatment of children with progressive or recurrent brain tumors with carboplatin or iproplatin: a Pediatric Oncology Group randomized phase II study. J Clin Oncol 10(2):249–256

    CAS  PubMed  Google Scholar 

  35. Soffietti R, Nobile M, Ruda R et al (2004) Second-line treatment with carboplatin for recurrent or progressive oligodendroglial tumors after PCV (procarbazine, lomustine, and vincristine) chemotherapy: a phase II study. Cancer 100(4):807–813

    Article  CAS  PubMed  Google Scholar 

  36. Friedman HS, Lovell S, Rasheed K, Friedman AH (1998) Treatment of adults with progressive oligodendroglioma with carboplatin (CBDCA): preliminary results. Writing committee for the brain tumor center at Duke. Med Pediatr Oncol 31(1):16–18

    Article  CAS  PubMed  Google Scholar 

  37. Kaloshi G, Sierra del Rio M, Ducray F et al (2010) Nitrosourea-based chemotherapy for low grade gliomas failing initial treatment with temozolomide. J Neurooncol 100(3):439–441

    Article  CAS  PubMed  Google Scholar 

  38. Reardon DA, Desjardins A, Vredenburgh JJ et al (2012) Phase II study of Gleevec plus hydroxyurea in adults with progressive or recurrent low-grade glioma. Cancer 118(19):4759–4767

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Chamberlain MC (2002) Salvage chemotherapy with CPT-11 for recurrent oligodendrogliomas. J Neurooncol 59(2):157–163

    Article  PubMed  Google Scholar 

  40. Taillibert S, Vincent LA, Granger B et al (2009) Bevacizumab and irinotecan for recurrent oligodendroglial tumors. Neurology 72(18):1601–1606

    Article  CAS  PubMed  Google Scholar 

  41. Chamberlain MC, Kormanik PA (1997) Salvage chemotherapy with paclitaxel for recurrent oligodendrogliomas. J Clin Oncol 15(12):3427–3432

    CAS  PubMed  Google Scholar 

  42. van den Bent MJ, Afra D, de Witte O et al (2005) Long-term efficacy of early versus delayed radiotherapy for low-grade astrocytoma and oligodendroglioma in adults: the EORTC 22845 randomised trial. Lancet 366(9490):985–990

    Article  PubMed  Google Scholar 

  43. Karim AB, Afra D, Cornu P et al (2002) Randomized trial on the efficacy of radiotherapy for cerebral low-grade glioma in the adult: European organization for research and treatment of cancer study 22845 with the medical research council study BRO4: an interim analysis. Int J Radiat Oncol Biol Phys 52(2):316–324

    Article  PubMed  Google Scholar 

  44. Hanzely Z, Polgar C, Fodor J et al (2003) Role of early radiotherapy in the treatment of supratentorial WHO Grade II astrocytomas: long-term results of 97 patients. J Neurooncol 63(3):305–312

    Article  PubMed  Google Scholar 

  45. Combs SE, Ahmadi R, Schulz-Ertner D, Thilmann C, Debus J (2005) Recurrent low-grade gliomas: the role of fractionated stereotactic re-irradiation. J Neurooncol 71(3):319–323

    Article  CAS  PubMed  Google Scholar 

  46. Combs SE, Thilmann C, Edler L, Debus J, Schulz-Ertner D (2005) Efficacy of fractionated stereotactic reirradiation in recurrent gliomas: long-term results in 172 patients treated in a single institution. J Clin Oncol 23(34):8863–8869

    Article  PubMed  Google Scholar 

  47. Shepherd SF, Laing RW, Cosgrove VP et al (1997) Hypofractionated stereotactic radiotherapy in the management of recurrent glioma. Int J Radiat Oncol Biol Phys 37(2):393–398

    Article  CAS  PubMed  Google Scholar 

  48. Hara A, Nishimura Y, Sakai N, Yamada H, Yanagawa S (1995) Effectiveness of intraoperative radiation therapy for recurrent supratentorial low grade glioma. J Neurooncol 25(3):239–243

    Article  CAS  PubMed  Google Scholar 

  49. McCormack BM, Miller DC, Budzilovich GN, Voorhees GJ, Ransohoff J (1992) Treatment and survival of low-grade astrocytoma in adults—1977–1988. Neurosurgery 31(4):636–642

    Article  CAS  PubMed  Google Scholar 

  50. Forsyth PA, Kelly PJ, Cascino TL et al (1995) Radiation necrosis or glioma recurrence: is computer-assisted stereotactic biopsy useful? J Neurosurg 82(3):436–444

    Article  CAS  PubMed  Google Scholar 

  51. Schmidt MH, Berger MS, Lamborn KR et al (2003) Repeated operations for infiltrative low-grade gliomas without intervening therapy. J Neurosurg 98(6):1165–1169

    Article  PubMed  Google Scholar 

  52. Steiger HJ, Markwalder RV, Seiler RW, Ebeling U, Reulen HJ (1990) Early prognosis of supratentorial grade 2 astrocytomas in adult patients after resection or stereotactic biopsy. An analysis of 50 cases operated on between 1984 and 1988. Acta Neurochir 106(3–4):99–105

    Article  CAS  PubMed  Google Scholar 

  53. Scopece L, Franceschi E, Cavallo G et al (2006) Carboplatin and etoposide (CE) chemotherapy in patients with recurrent or progressive oligodendroglial tumors. J Neurooncol 79(3):299–305

    Article  CAS  PubMed  Google Scholar 

  54. Brandes AA, Basso U, Vastola F et al (2003) Carboplatin and teniposide as third-line chemotherapy in patients with recurrent oligodendroglioma or oligoastrocytoma: a phase II study. Ann Oncol 14(12):1727–1731

    Article  CAS  PubMed  Google Scholar 

  55. Streffer J, Schabet M, Bamberg M, Grote EH, Meyerman R, Voigt K, Dicgans J, Weller M (2000) A role for preirradiation PCV chemotherapy for oligodendroglial brain tumors. J Neurooncol 247(4):297–302

    CAS  Google Scholar 

  56. Reyes-Mugica M, Rieger-Christ K, Ohgaki H, Ekstrand BC, Helie M, Kleinman G, Yahanda A, Fearon ER, Kleihues P, Reale MA (1997) Loss of DCC expression and glioma progression. Cancer Res 57(3):382–386

    Google Scholar 

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Acknowledgments

We acknowledge the significant contributions of Laura Mitchell, Senior Manager of Clinical Practice Guidelines for the CNS, and also the AANS/CNS Joint Guidelines Committee (JGC) for their review, comments and suggestions, as well as Anne Woznica, Medical Research Librarian.

Disclosures

Dr. Batchelor is a consultant for EMD-Serono. Dr. Kalkanis is a consultant for Arbor and Varian. Dr. Olson is a consultant for the American Cancer Society; has received research funding from the National Cancer Institute, Genentech, and Millenium; and has received investigational drug provision from Merck.

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Authors and Affiliations

  1. Department of Neurosurgery, Massachusetts General Hospital, 15 Parkman Street, Wang 745, Boston, MA, 02114, USA

    Brian V. Nahed

  2. Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA

    Navid Redjal

  3. Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA

    Daniel J. Brat

  4. Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY, USA

    Andrew S. Chi & Tracy T. Batchelor

  5. Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA

    Kevin Oh

  6. Department of Neurosurgery, Kansas University Medical Center, Kansas City, KS, USA

    Timothy C. Ryken

  7. Department of Neurosurgery, Henry Ford Health System, Detroit, MI, USA

    Steven N. Kalkanis

  8. Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, USA

    Jeffrey J. Olson

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  1. Brian V. Nahed
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Correspondence to Brian V. Nahed.

Additional information

Brian V. Nahed and Navid Redjal are co-first authors.

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Nahed, B.V., Redjal, N., Brat, D.J. et al. Management of patients with recurrence of diffuse low grade glioma. J Neurooncol 125, 609–630 (2015). https://doi.org/10.1007/s11060-015-1910-2

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  • DOI: https://doi.org/10.1007/s11060-015-1910-2

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