Case presentation the modern management of oligodendrogliomas
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Case Presentation: The modern management of oligodendrogliomas. James Manfield B.S. University College London. Background. Pt 25 y/o male marine CC First seizure HPC Otherwise well. No abnormal findings o/e. No significant PHM, FHM, DH, SH.

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Case Presentation: The modern management of oligodendrogliomas

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Case presentation the modern management of oligodendrogliomas

Case Presentation:The modern management of oligodendrogliomas

James Manfield B.S.

University College London


Background

Background

  • Pt 25 y/o male marine

  • CC First seizure

  • HPC Otherwise well. No abnormal findings o/e. No significant PHM, FHM, DH, SH.

  • Underwent biopsy  low-grade oligodendroglioma (1p19q not initially requested)

  • Referred to Dr. Wenke for debulking.

  • Successful stereotactic volumetric resection c. iop CT leaving 1 cm margins.


Pre op imaging

Pre-op imaging


Oligodendrogliomas

Oligodendrogliomas

  • Primary glial brain tumors. Grade II and Grade III (anaplastic)

  • Aetiology poorly understood

  • 5-19% of all intracranial tumors; 25% of all gliomas. M:F 2:1. Median age at D. 40-50 years.

  • Most common CC seizure (low grade), focal deficits, ↑ICP or cognitive deficits (high grade).


1p 19q why does it matter

1p/19q: Why does it matter?

  • 1p/19q co-deletion, mediated by an unbalanced translocation of 19p to 1q.

  • Combined loss present in 60-70% of all ODs (Smith et al. 2000)

  • 1st CNS neoplasm in which a better genetic signature was correlated with outcome in phase III trials (Cairncross et al. 2006, Van den Bent et al. 2006).


Summary of data

Summary of data

  • Low grade OD/OA median 11.9 years with codeletion vs. 10.3 without [Shaw et. al 2002]

  • 5 years survival 50% higher [Fontaine et al 2008]. Confounding variables.

  • EORTC 26951: AOD 6-7 years c. co-deletion vs. 2-2.8 without combined loss [Cairncross et al. 2006, van den Bent et al. 2006].

  • 1p19q found to be most powerful predictor of outcome [Kouwenhoven et al. 2009].

  • Multiple studies now consistently show longer survival time.

  • Not prognostic but predictive [Weller et al. 2007]


Management surgery

Management: Surgery

  • 3 aims: tissue, mass effect ?better px

  • No RCT data

  • Retrospective study data has limitations

  • 1 uncontrolled study- complete resection in low-grade OD associated with longer disease-free intervals [Berger et al. 1994].

  • Another study- subtotal resection improves survival [Shaw et al. 1997]

  • In contrast other studies looking at gross total resection have shown no survival benefit [Daumas-Duport 1997 & Kros et al. 1994].

  • Nevertheless remains the standard of care.


Management radiotherapy

Management: Radiotherapy

Low grade

  • One large study on early vs. delayed RT observed an improved progression-free survival after early RT but no increase in overall survival [van den Bent 2005]

    Anaplastic

  • Mixed results

  • 1p19q status relevant


Management chemotherapy

Management: Chemotherapy

  • PCV original regimen

    2/3 of patients with recurrent OD have either a CR or PR to PCV. TtP around 12-18 months [Sofietti R et al 1998].

  • AOD [Van den Bent 2008] 2 RCTs:

  • Temozolomide- 2 large phase II trials. Clear alternative. No formal comparison between TMZ and PCV.


Discussion

Discussion

  • Cochrane Review: 2 RCTs. PCV + RT + surgery vs RT + surg- PCV delays progression, no effect on overall survival. [PCV haematological toxicity].

  • RCTs confirmed the major predictive role of 1p/19q status.

  • 1p/19q status predicts more indolent behaviour and longer progression free survival after chemo or radiotherapy [Cochrane Review 2008].

  • Appears to apply to both low grade and high grade tumors, although limited data in low grade ODs [Van den Bendt 2008]

  • Limitations of 1p/19q: With absent co-deletions still 33% show chemo response [Fontaine et al, 2008]

  • Predictive for response to both RT and chemo therefore not appropriate to differentiate.


Optimal management for our patient

Optimal management for our patient

  • What to do with a young patient, low grade tumor presenting with seizure.

  • Many treatment modalities available- given length of expected survival must consider late sequalae.

  • Debulking reasonable. Insufficient evidence to justify the risks of aggressive resection.

  • RT- cognitive decline etc. Without good RCT evidence otherwise prudent to observe and delay until progression.

  • Wish to delay RT major rationale for upfront chemotherapy- but no randomized data. Local side effects of 6 weeks RT vs systemic side effects 1 year chemotherapy. Ongoing EORTC trial.

  • 1p19q status may be useful. Potentially renders role of surgery less important. Consider early TMZ delaying RT.


Summary

Summary

  • OD tumors remain ultimately fatal

  • Lack of randomized data for optimal management.

  • With longer survival QOL issues and delayed side effects must be considered.

  • 1p19q co-deletion implies better outcome.

  • Predictive, not prognostic. Absence also does not exclude response.

  • A number of questions remain.


References

References

  • Smith JS, Perry A, Borell TJ, at al. Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas. J Clin Oncol. 2000 Feb;18(3):636-45.

  • Cairncross G, Berkey B, Shaw E, et al. 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 2006 Jun 20;24 (18):2707-14.

  • van den Bent MJ, Carpentier AF, Brandes AA, et al. 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. 2006 Jun 20;24(18):2715-22.

  • Shaw E, Arusell R, Scheithauer B, et al. Prospective randomized trial of low- versus high-dose radiation therapy in adults with supratentorial low-grade glioma: initial report of a North Central Cancer Treatment Group/Radiation Therapy Oncology Group/Eastern Cooperative Oncology Group study. J Clin Oncol. 2002 May 1;20(9):2267-76.

  • Fontaine D, Vandenbos F, Lebrun C, et al. Diagnostic and prognostic values of 1p and 19q deletions in adult gliomas: critical review of the literature and implications in daily clinical practice. Rev Neurol (Paris). 2008 Jun-Jul;164(6-7):595-604. Epub 2008 May 21.

  • Kouwenhoven MC, Gorlia T, Kros JM, et al. Molecular analysis of anaplastic oligodendroglial tumors in a prospective randomized study: A report from EORTC study 26951. Neuro Oncol. 2009 Dec;11(6):737-46.

  • Weller M, Berger H, Hartmann C, et al. Combined 1p/19q loss in oligodendroglial tumors: predictive or prognostic biomarker? Clin Cancer Res. 2007 Dec 1;13(23):6933-7.

  • Berger MS, Deliganis AV, Dobbins J, Keles GE. The effect of extent of resection on recurrence in patients with low grade cerebral hemisphere gliomas. Cancer. 1994 Sep 15;74(6):1784-91.

  • Daumas-Duport C, Tucker ML, Kolles H, et al. Oligodendrogliomas. Part II: A new grading system based on morphological and imaging criteria. J Neurooncol. 1997 Aug;34(1):61-78.

  • Kros JM, Pieterman H, van Eden CG, Avezaat CJ. Oligodendroglioma: the Rotterdam-Dijkzigt experience. Neurosurgery. 1994 Jun;34(6):959-66; discussion 966.

  • van den Bent MJ, Afra D, de Witte O, et al. Long-term efficacy of early versus delayed radiotherapy for low-grade astrocytoma and oligodendroglioma in adults: the EORTC 22845 randomised trial. Lancet. 2005 Sep 17-23;366(9490):985-90.


References cont

References cont.

  • Soffietti R, Rudà R, Bradac GB, Schiffer D. PCV chemotherapy for recurrent oligodendrogliomas and oligoastrocytomas. Neurosurgery. 1998 Nov;43(5):1066-73.

  • Van den Bent MJ, Reni M, Gatta G, Vecht C. Oligodendroglioma. Crit Rev Oncol Hematol. 2008 Jun;66(3):262-72. Epub 2008 Feb 12.

  • Quon H, Abdulkarim B. Adjuvant treatment of anaplastic oligodendrogliomas and oligoastrocytomas. Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No.: CD007104. DOI: 10.1002/14651858.CD007104.


Thank you

Thank you!

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