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.
• 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
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 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
• 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
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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
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
• 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
• 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
• 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
• 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
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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 JunJul;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 1723;366(9490):985-90.
References cont.
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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!
• Questions?