Low grade oligodendroglioma

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Low grade oligodendroglioma

  1. 1. EVIDENCE BASED SURGERY MEETING “ CURRENT TREND IN TREATMENT OF LOW GRADE OLIGODENDROGLIOMA ” Sanmugarajah Paramasvaran 12 th May 2011
  2. 2. <ul><li>Case </li></ul><ul><li>32 yr/ Male </li></ul><ul><li>Generalised seizure </li></ul><ul><li>MRI - left parieto-occipital lesion </li></ul><ul><li>Biopsy – low grade oligodendroglioma </li></ul><ul><li>Studies for 1P/19Q – loss of heterozygosity </li></ul>
  3. 4. Clinical Question What are the current treatment option for low grade oligodendroglioma and significance of loss of hetrozygosity ?
  4. 5. Search Strategy P – pts with low grade oligodendroglioma I – excision C –observation / excision with radiotherapy and or chemotherapy O – prolonged survival / recurrence free period
  5. 6. <ul><li>Databases </li></ul><ul><li>Medline – using MeSH </li></ul><ul><li>Scopus - using keywords </li></ul><ul><li>Cochrane – for systemic review and clinical trial </li></ul><ul><li>Keywords </li></ul><ul><li>“ oligodendroglioma” “low grade” “treatment” </li></ul>
  6. 7. Medline Ovid Search
  7. 8. Scopus Search
  8. 9. Cochrane Search
  9. 10. <ul><li>Medline </li></ul><ul><li>64 articles. </li></ul><ul><li>7 highly relevant. </li></ul><ul><li>Scopus </li></ul><ul><li>31 articles total. </li></ul><ul><li>further 2 highly relevant. </li></ul><ul><li>Cochrane </li></ul><ul><li>No reviews </li></ul><ul><li>No clinical trials </li></ul>
  10. 11. Defer treatment <ul><li>Suspected Low - grade Glioma : Is defering treatment safe? </li></ul><ul><li>- Lawrence et al, Annals of Neurol 1992:31: 431-436 </li></ul><ul><li>26 pts WAIT group, 20 pts NOWAIT group </li></ul><ul><li>Criteria: seizure / no neurolgy / unenhancing mass / only anti-epileptic </li></ul><ul><li>No difference to progression time (56 months) </li></ul>
  11. 12. Treatment of low grade oligodendroglioma without radiotherapy <ul><li>Higuchi et al, Neurology 63(12) 2384-6, 2004 Dec </li></ul><ul><li>18 pts </li></ul><ul><li>Followed up after total resection or chemo after subtotal resection / biopsy </li></ul><ul><li>94% were progression free at 4.7 yrs </li></ul>
  12. 13. Phase ll trial of Procarbazine,Lomustine, and Vincristine as Initial Therapy for patients with Low-Grade astrocytoma: Efficacy and Associations With Chromosomal Abnormalities <ul><li>Jan C. Buckner et al , Mayo Clinic </li></ul><ul><li>Journal of Clinical Oncology,2003 12(2): 251-255 </li></ul><ul><li>Response, toxicity and corelations with 1p/19q deletions </li></ul><ul><li>Prospective </li></ul><ul><li>28 patients, Had biopsy / subtotal resection </li></ul><ul><li>PCV 6 cycles + RT </li></ul><ul><li>Before RT - 29% had regression, 61% stable, 11% progression </li></ul><ul><li>With RT 52% had radiological improvement </li></ul><ul><li>Toxicity: 75% grade 3-4 leukopenia </li></ul><ul><li>No evidence of response association to 1p/19q loss </li></ul>
  13. 14. Successful treatment of LG oligodendroglial tumours with a chemotherapy regimen of PCV <ul><li>Elize M Biemond-ter stege et al </li></ul><ul><li>Cancer, 2005 : (103):4, 802-9 </li></ul><ul><li>Retrospective,1998 - 2004 </li></ul><ul><li>16 patients with newly diagnosed LGO </li></ul><ul><li>6 cycles </li></ul><ul><li>13 patients showed radiological response </li></ul><ul><li>7 patiens had combined loss 1p,19q </li></ul><ul><li>3 patients – bone marrow toxicity, 3 – hepatotoxicity </li></ul>
  14. 15. Temozolamide as Initial Treatment for Adults With LGO or Oligoastrocytoma and Correlation With Chromosome 1p Deletion <ul><li>K. Hoang – Xuan et al </li></ul><ul><li>Journal of Clinical Oncology,2004, 22(15):3133 – 3138 </li></ul><ul><li>Response to TMZ and predictive value of 1p deletion </li></ul><ul><li>Prospective, 60 patients </li></ul><ul><li>Median no of cycles : 11 </li></ul><ul><li>31% radiological response, 51% clinical response, particularly with seizures </li></ul><ul><li>8% myelosuppression </li></ul><ul><li>Loss of 1p - 50% had objective response, 50% had stable </li></ul><ul><li>disease, no progression </li></ul>
  15. 16. Progressive low Grade oligodendroglioma response o TMZ and corelation between Genetic Profile and MGMT Protein expression <ul><li>Netta Levin et al </li></ul><ul><li>Cancer, 2006, 106 (8) 1759-1764 </li></ul><ul><li>28 patients , had biopsy or surgery, no RT </li></ul><ul><li>12 had seizure progression </li></ul><ul><li>Median treatment duration was 12.5 months </li></ul><ul><li>53% clinical improvement, 61% radiological improvement </li></ul>
  16. 17. <ul><li>10 pts had 1p19q loss, 9 showed radiological response, 1 stable </li></ul><ul><li>Only 33% had MGMT levels studied </li></ul><ul><li>In loss of 1p, statistically significant lower MGMT levels </li></ul>
  17. 18. REVIEW ARTICLE <ul><li>Oligodendroglial tumours </li></ul><ul><li>- Sajeel Chowdhary et al, Expert review of Neurotherapeutics,6(4) : 519-532, 2006 </li></ul><ul><li>21% minimal contrast enhancement </li></ul><ul><li>Median survival after GTR/STR with radiotherapy - 7.3 yrs </li></ul><ul><li>No controlled , prospective trial comparing observation and surgery </li></ul><ul><li>Short preop seizure ( < 1 year ) ,near complete / total excision Resection of seizure focus </li></ul><ul><li>EORTC trials showed extent of resection favoured better outcome </li></ul>
  18. 19. <ul><li>Van den Bent et al (2002) , with randomized prospective study on post op radiotherapy </li></ul><ul><li>With RT , PFS was 5.3 yrs and no RT ,3.4yrs </li></ul><ul><li>With RT , OS was 7.4 yrs and no RT, 7.2 yrs </li></ul><ul><li>Kiebert et al (EORTC 22844)(1998) </li></ul><ul><li>- long term effect of cognitive decline </li></ul>
  19. 20. <ul><li>Eyre et al (1993) – randomized trial on adjuvant chemo in incomplete excision </li></ul><ul><li>no survival advantage </li></ul><ul><li>Buckener et al (2003), Phase ll trial of PCV </li></ul><ul><li>Loss of 1P,19Q no response </li></ul>
  20. 21. Review Article Low Grade oligodendroglioma: Current trend and future hopes <ul><li>Zarnie et al, Expert Review of Anticancer Therapy, Nov 2009 </li></ul><ul><li>SURGERY </li></ul><ul><li>NO PROSPECTIVE RANDOMIZED TRIAL – BIOPSY VS GTR </li></ul><ul><li>Claus et al in 2005 reported a retrospective study of 156 pts undergoing intra-op guided resection. </li></ul><ul><li>Pts with STR 1.4 X of recurrence, 4.9 X of death </li></ul>
  21. 22. <ul><li>STEREOTACTIC SURGERY FOR DEEP OR ELOQUENT LOCATION </li></ul><ul><li>Small low grade gliomas with only seizure - </li></ul><ul><li>management controversial </li></ul>
  22. 23. <ul><li>RADIOTHERAPY </li></ul><ul><li>EORTC prospective randomized trial, 1986-1997 </li></ul><ul><li>No difference in 5 yrs overall survival in complete/ incompletely resected tumours </li></ul><ul><li>Withold in young pts, minimal post op residual </li></ul><ul><li>Give with tumour progression </li></ul>
  23. 24. <ul><li>CHEMOTHERAPY </li></ul><ul><li>RTOG 9802 STUDY - </li></ul><ul><li>in patients poor prognosis, PCV reduced the risk </li></ul><ul><li>of death by 48% and progression by 55% </li></ul><ul><li>Temozolamide </li></ul><ul><li>- MGMT hypermethylation more frequently with </li></ul><ul><li>1p/ 19q loss </li></ul>
  24. 25. CONCLUSION <ul><li>No class 1 evidence regarding surgery </li></ul><ul><li>Defer for small asymptomatic lesion </li></ul><ul><li>Symptomatic , other than, seizure – resect </li></ul><ul><li>Progressive tumour – add RT </li></ul><ul><li>In 1p/19q loss – TMZ? </li></ul>

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