Oligodendrogliomas are common intra-axial primary brain tumours, and carry special significance due to several key features, which when present provide better prognosis compared to other intra-axial tumours. One of these features is presence of 1p/19q chromosomal codeletion that seems to not only be a marker of better prognosis but also signifies better response to chemotherapy. Herein the authors review the literature for evidence of the prognostic value of 1p/19q codeletion in OD

Khalid, Muhammad Usman

Laghari, Altaf Ali

Qadeer, Namra

Shamim, Muhammad Shahzad

English

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eCommons@AKUSection of Neurosurgery Department of SurgeryJanuary 2018Prognostic value of 1p/19q chromosomalcodeletion in patients with oligodendrogliomaAltaf Ali LaghariAga Khan University, altaf.alilaghari@aku.eduUsman KhalidAga Khan UniversityNamra QadirAga Khan UniversityMuhammad Shahzad ShamimAga Khan University, shahzad.shamim@aku.eduFollow this and additional works at: https://ecommons.aku.edu/pakistan_fhs_mc_surg_neurosurgRecommended CitationLaghari, A., Khalid, U., Qadir, N., Shamim, M. (2018). Prognostic value of 1p/19q chromosomal codeletion in patients witholigodendroglioma. Journal of the Pakistan Medical Association, 69(1), 132-134.Available at: https://ecommons.aku.edu/pakistan_fhs_mc_surg_neurosurg/174AbstractOligodendrogliomas are common intra-axial primarybrain tumours, and carry special significance due toseveral key features, which when present provide betterprognosis compared to other intra-axial tumours. One ofthese features is presence of 1p/19q chromosomal co-deletion that seems to not only be a marker of betterprognosis but also signifies better response tochemotherapy. Herein the authors review the literaturefor evidence of the prognostic value of 1p/19q co-deletion in OD.Keywords: Glioma, Oligodendroglioma,chemotherapy.IntroductionOligodendrogliomas (OD) account for 10% of all gliomasand 4% of all primary brain tumours.1 They are diffuselyinfiltrating tumours, arising from the white matter ofcerebral hemispheres. These tumours characteristicallyshow better prognosis compared to most other gliomas,especially in the presence of certain features such asyoung age at presentation, good performance status atpresentation and after surgery, frontal location,andcombined loss of 1p/19q.2 1p/19q chromosomal co-deletion seems to not only be a marker of betterprognosis but also signifies increased response toadjuvant therapy with selective drugs.3,4 Longerprogression free survival (PFS) has been noted amongstpatients who had been treated for a confirmed 1p/19q co-deleted OD, although improvement in overall survival(OS) has not been definitively established. Geneticanalysis of these tumours is now recognized at the basisfor classification of tumour type, and for the prediction ofbiological behaviour, and response to therapeuticmodalities. There is extensive literature and numerousclinical trials exploring the relationship betweenprognosis of OD with 1p/19q co-deletion. This reviewfocuses on a few of these articles to provide a brief yetholistic picture on the topic.Review Of EvidenceAs early as 2000, Smith et al., demonstrated that 1p/19qchromosomal loss in pure OD was a statistically significantindicator of prolonged survival.5 Cairncross et al. 6, did anexhaustive research on 289 patients diagnosed withanaplastic OD and their response to radiotherapy (RT)alone compared to RT with procarbazine, lomustine, andvincristine (PCV) chemotherapy with the conclusion thatPCV with RT did not prolong survival.6 Jenkins et al.,thenthrough sequencing and following up 119 patients,predicted a better overall survival of approximately  oneyear for patients with low grade OD featuring 1p/19q co-deletion or translocation, especially those who receivedhigher doses of RT.7 Van den Brent et al., also conducted amajor study in 2006 with a total of 368 patients withanaplastic OD enrolled and followed up for a median ofJ Pak Med Assoc132EVIDENCE BASED NEURO-ONCOLOGYPrognostic value of 1p/19q chromosomal codeletion in patients witholigodendrogliomaAltaf Ali Laghari, Muhammad Usman Khalid, Namra Qadeer, Muhammad Shahzad ShamimDepartment of Surgery, Section of Neurosurgery, Aga Khan UniversityHospital, Karachi. Pakistan.Correspondence: Muhammad Shahzad Shamim.Email: shahzad.shamim@aku.eduFigure-1(a): MRI T1WI with contrast showing a heterogeneously enhancingoligodendroglioma in right temporoparietal region.60 months.8 Patients were either given 33 cycles of RT orPCV with RT, OS was significantly higher in RT with PCVtherapy although 36% of patients had to discontinue PCVdue to toxicity. They concluded that although overallsurvival was unchanged, progression-free survival wassignificantly better in patients who had OD with 1p/19qchromosomal co-deletion. In 2012 Yip et al., furtheranalyzed chromosomal mutations of 1p/19q and genesencoding isocitrate dehydrogenase (IDH) as diagnosticmarkers for ODs.9 Lecavalier-Barsoumet al., in 2014,systematically reviewed treatment modalities foranaplastic oligodendrogliomas with the aim ofestablishing the predictive and prognostic value ofmarkers such as 1p/19q co-deletion.10 To this effect PCVprior to RT increased mean overall survival, with thesubset of ODs with 1p/19q chromosomal codeletionshowing increased sensitivity to combined PCV with RT.However, grade 3 and 4 toxicities were noted with PCVtherapy and a conclusive replacement withtemozolomide was unable to be ascertained. Li et al.,in2014 again, studied and followed a 100 cases of OD andwere able to associate 1p/19q loss, as well as Sox-17protein, to better prognosis.11 Sabha et al.,alsoinvestigated a cohort of 108 non-enhancing hemisphericgrade II-III gliomas with results indicating that 1p/19q losswas predictive of overall survival but not progression freesurvival.12 Interestingly IDH mutation was shown to beindicative of both and merits further studies. In 2016,Hataet al.,retrospectively analyzed the long-termoutcome of a case series (36 patients) with OD treatedwith RTand procarbazine, nimustine, vincristine (PAV)therapy.3 Their results showed that IDH mutation and1p/19q loss were the prognostic factors to consider forOD, not WHO grade, furthermore there was a significantlybetter prognosis for patients with 1p/19q co-deletion. In2017 Hacisalihogluet al., followed through with aretrospective analysis of 41 anaplastic OD cases, 35patients received standard radiotherapy whilst 26patients then underwent additional chemotherapy withtemozolomide.2 In the 19 patients who had chromosomal1p/19 co-deletion, progression free survival was noted tobe significantly higher, regardless of treatment modality.Lastly McNamraet al., did a retrospective analysis on 106patients in 2017 to determine treatment outcomes inpatients diagnosed with gliomas with full or partial1p/19q codeletion.13 Of these patients, 66% had full1p/19q chromosomal co-deletion and these were foundto have better progression free survival than those withno co-deletion or 1p or 19q codeletion  alone. In additionupfront therapy (in some cases with temozolamide alone)was found to have prognostic value similar to 1p/19q co-deletion.ConclusionChromosomal codeletion of 1p/19q is predictive of afavourable prognosis for patients regardless of treatment.Presence of co-deletion however is particularly indicativeof sensitivity to PCV therapy, in conjunction withradiotherapy. Temozolomide is a promising alternative toPCV but as of this moment in time its efficacy comparedto PCV in OD with 1p/19q co-deletion is not wellestablished. In addition, studies seem split on whether1p/19q loss provides better overall survival or progressionfree survival though most studies do point towards thelatter. References1. MirzaFA, Shamim MS. Extent of resection and timing of surgery inadult low grade glioma. J Pak Med Assoc 2017; 67: 959-961.2. Hacisalihoglu P, Kucukodaci Z, Gundogdu G, Bilgic B. The correlationbetween 1p/19q codeletion, IDH1 mutation, p53 overexpressionand their prognostic roles in 41 Turkish anaplasticoligodendroglioma patients. TURK NEUROSURG . 2017;27:682-9. 3. Hata N, Yoshimoto K, Hatae R, Kuga D, Akagi Y, Suzuki SO, et al.Deferred radiotherapy and upfront procarbazine-ACNU-vincristineadministration for 1p19q codeleted oligodendroglial tumors areassociated with favorable outcome without compromising patientperformance, regardless of WHO grade. Onco Targets Ther.2016;9:7123-31. 4. Van den Bent MJ, Reni M, Gatta G, Vecht C. Oligodendroglioma. Crit Rev Oncol Hematol . 2008;66:262-72. 5. Smith JS, Perry A, Borell TJ, Lee HK, O'Fallon J, Hosek SM, et al.Alterations of chromosome arms 1p and 19q as predictors of survivalin oligodendrogliomas, astrocytomas, and mixedVol. 69, No. 1, January 2019Prognostic value of 1p/19q chromosomal codeletion in patients with oligodendroglioma 133Figure-1(b): Post-operative MRI T1WI with contrast scan of the same patient showingmaximal safe resection.oligoastrocytomas. J. Clin. Oncol: official journal of the AmericanSociety of Clinical Oncology. 2000;18:636-45. 6. Cairncross G, Berkey B, Shaw E, Jenkins R, Scheithauer B, BrachmanD, et al. Phase III trial of chemotherapy plus radiotherapy comparedwith radiotherapy alone for pure and mixed anaplasticoligodendroglioma: Intergroup Radiation Therapy Oncology GroupTrial 9402. J. Clin. Oncol: official journal of the American Society ofClinical Oncology. 2006;24:2707-14. 7. Jenkins RB, Blair H, Ballman KV, Giannini C, Arusell RM, Law M, et al.A t(1;19)(q10;p10) mediates the combined deletions of 1p and 19qand predicts a better prognosis of patients with oligodendroglioma.Cancer Res. 2006;66:9852-61. 8. Van den Bent MJ, Carpentier AF, Brandes AA, Sanson M, TaphoornMJ, Bernsen HJ, et al. Adjuvant procarbazine, lomustine, andvincristine improves progression-free survival but not overallsurvival in newly diagnosed anaplastic oligodendrogliomas andoligoastrocytomas: a randomized European Organisation forResearch and Treatment of Cancer phase III trial. J. Clin. Oncol: officialjournal of the American Society of Clinical Oncology. 2006;24:2715-22. 9. Yip S, Butterfield YS, Morozova O, Chittaranjan S, Blough MD, An J, etal. Concurrent CIC mutations, IDH mutations, and 1p/19q lossdistinguish oligodendrogliomas from other cancers. J PATHOL.2012;226:7-16. 10. Lecavalier-Barsoum M, Quon H, Abdulkarim B. Adjuvant treatmentof anaplastic oligodendrogliomas and oligoastrocytomas. CochraneDatabase Syst Rev2014:CD007104. 11. Li J, Miao N, Liu M, Cui W, Liu X, Li X, et al. Clinical significance ofchromosome 1p/19q loss of heterozygosity and Sox17 expression inoligodendrogliomas. Int J Clin Exp Pathol . 2014;7:8609-15. 12. Sabha N, Knobbe CB, Maganti M, Al Omar S, Bernstein M, Cairns R, etal. Analysis of IDH mutation, 1p/19q deletion, and PTEN lossdelineates prognosis in clinical low-grade diffuse gliomas.  NeuroOncol 2014;16:914-23. 13. McNamara MG, Jiang H, Lim-Fat MJ, Sahebjam S, Kiehl TR,Karamchandani J, et al. Treatment Outcomes in 1p19q Co-deleted/Partially Deleted Gliomas. Can J Neurol Sci. 2017;44:288-94.134 A.A. Laghari, M. U. Khalid, N.Qadeer, et al J Pak Med Assoc

Prognostic value of 1p/19q chromosomal codeletion in patients with oligodendroglioma

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Prognostic value of 1p/19q chromosomal codeletion in patients with oligodendroglioma

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