Low grade glioma is a group of WHO grade II tumours including diffuse astrocytoma, oligodendroglioma, and oligoastrocytoma. Strong evidence exists in literature now to support early surgery and higher extent of safe resection in improving outcomes. In this review, we are highlighting some of the important studies done in the last few years specifically addressing timing of surgery and extent of resection

Mirza, Farhan A.

Muhammad Shahzad Shamim,

English

eCommons@AKU

eCommons@AKUSection of Neurosurgery Department of SurgeryJune 2017Extent of resection and timing of surgery in adultlow grade gliomaFarhan A. MirzaAga Khan UniversityMuhammad Shahzad ShamimAga Khan University Hospital, shahzad.shamim@aku.eduFollow this and additional works at: http://ecommons.aku.edu/pakistan_fhs_mc_surg_neurosurgPart of the Neurology Commons, and the Surgery CommonsRecommended CitationMirza, F., Muhammad Shahzad Shamim, . (2017). Extent of resection and timing of surgery in adult low grade glioma. JPMA: Journalof the Pakistan Medical Association, 67(6), 959-961.Available at: http://ecommons.aku.edu/pakistan_fhs_mc_surg_neurosurg/58AbstractLow grade glioma is a group of WHO grade II tumoursincluding diffuse astrocytoma, oligodendroglioma, andoligoastrocytoma. Strong evidence exists in literaturenow to support early surgery and higher extent of saferesection in improving outcomes. In this review, we arehighlighting some of the important studies done in thelast few years specifically addressing timing of surgeryand extent of resection.Keywords: low grade glioma, extent of resection, earlysurgery, progression free survival, overall survivalIntroductionLow grade gliomas (LGG) are a group of slow growingWHO grade II tumours comprising of diffuseastrocytoma, oligodendroglioma and rarelyoligoastrocytoma. These tumours ultimately undergomalignant transformation and turn into higher gradetumours with poor outcome. Gemistocytic astrocytoma,despite being a grade II entity, is not included in thisgroup due to its unusual malignant behaviour. Lowgrade gliomas are infiltrative, often located in eloquentcortex, and are difficult to differentiate from normalbrain tissue on gross examination, which leads to theinherent difficulty in incompletely resecting theselesions. Introduction and popularization of the use ofIDH1 mutation status and 1p/19q co-deletion hasallowed better understanding of the behaviour of thesetumours and also for prediction of their malignantpotential. Early surgery versus observation, and extentof safe resection are questions that have beeninvestigated extensively for these tumours. A handful ofstudies in the last three decades have tried to addressthese questions for this subset of the glioma family.Operative adjuncts such as neuronavigation, awakecraniotomy, intra-operative mapping, intra operativeMRI (iMRI), functional MRI (fMRI), and fiber tractographyare now playing an important role in achieving betterextent of resection with safety, even near eloquentcortex. Review of EvidenceWe queried the PubMed database with the phrases'extent of resection in low grade glioma' and 'timing ofsurgery for low grade glioma'. Articles addressing thesetopics were reviewed.Timing of SurgeryThe incidence of low grade gliomas arose with the adventof computed tomography and improvement in imagingtechniques. Historically, with lesions incidentallydiscovered on imaging that resembled low grade gliomasor even those presenting with new onset seizures, a 'waitand observe' approach was taken. In some instancesstereotactic biopsy was performed to determine tissuediagnosis and then institute adjuvant therapy. Thisapproach was fraught with issues as most of thesetumours would progress and transform into higher grademalignant lesions, which is the natural history of theseentities. One of the first studies on this subject was aretrospective review in 1991 by Smith et al., on primarybrain tumours presenting with epilepsy.1 It had severallimitations in its methodology and failed to show anymeaningful difference in outcomes of early or latesurgery. Similar conflicting results were seen in the studyby van Weelen et al,. in 1998.2 Several studies in thesubsequent years were performed to understand besttreatment strategy for these low grade lesions, mainlyaddressing extent of resection. In 2012, the landmarkNorwegian study by Jakola et al., comprehensivelyanswered the question of upfront surgery vs. wait andwatch approach. Their population based analysis tookinto account the practice of two hospitals: one favouringearly biopsy and observe, whereas the other centerfavoured upfront resection in a homogenous patientpopulation. Overall survival was significantly better withearly surgical resection (P=0.01). Median survival was 5.9years (95% CI, 4.5-7.3) with biopsy only while mediansurvival was not reached in the group with earlyresection. Estimated 5-year survival was 60% (95% CI,48%-72%) for biopsy and 74% for (95% CI, 64%-84%)early resection.3 Majority of the patients included wereJ Pak Med Assoc959EVIDENCE BASED NEURO-ONCOLOGYExtent of resection and timing of surgery in adult low grade gliomaFarhan A. Mirza,1Muhammad Shahzad Shamim21Department of Neurosurgery, University of Kentucky, Lexington, KY, USA,2Department of Surgery, Section of Neurosurgery, Aga Khan UniversityHospital, Karachi, Pakistan.Correspondence:Muhammad Shahzad Shamim.Email: shahzad.shamim@aku.edufound to have grade II astrocytoma. This was furtherstudied in their post hoc analysis, revealing similarresults with early surgery.Extent of ResectionIn 1993, Philippon et al., published a retrospectiveanalysis of their experience and documented 80% 5year survival with gross total resection (GTR) and 50%with subtotal resection (STR).4 Van Weelen et al., in 1998published their volumetric results with 62% 5 yearsurvival with >75% resection and 18% survival in <75%resection.2 Smith et al in 2008 further elaborated oncorrelation of volumetric extent of resection and noted97% 5 year survival rate with 90-99% resection. Theyalso correlated increased malignant progression freesurvival (MPFS) with greater EOR.5 In this large series,the authors also noted that large tumours on pre-operative scans, despite extent of resection, wereassociated with lower OS, PFS and MPFS. Similarly,McGirt et al., published their series the same yearshowing 95% 5 year survival with gross total resection(GTR), 80% 5 year survival with near total resection(NTR) and 70% survival with subtotal resection (STR),based on residual FLAIR abnormalities on post-operative T2 MRI. They documented increasedmalignant progression free survival (MPFS) with GTR.6Concept of Supratotal ResectionThe concept of cancer free margins is wellestablished in solid organ surgery. In brain surgery,however, this can seldom be achieved given theeloquent nature of white matter tracts adjacent tothe tumour even in presumably 'non-eloquent'regions of the brain. Employing the advantage ofawake craniotomy with intra-operative cortical andsubcortical mapping, Duffau and colleagues havevery elegantly elaborated on the concept ofsupratotal resection, or negative marginneurosurgery in select patients.9 In their series from2011, they performed supratotal resection in 15patients with dominant left hemisphere non-eloquent region low grade glioma. Supratotalresection was performed, with 60% of the patientsexperience transient post-operative deficits withcomplete resolution. Compared to their comparableseries of gross total resection, the supratotalresection group had lower rates of recurrencewithout malignant transformation. Despite the smallnumbers, this concept has had a profoundimplication on glioma surgery. Duffau and colleagueshave since published extensively on this philosophyand their results with low grade gliomas surpass theresults of any other center. Their work has alsoallowed us to better understand the behaviour of lowgrade gliomas and the cyto-architectural andfunctional changes in the brain associated with theprogression of these lesions.ConclusionOverwhelming evidence suggests that upfront surgicalresection instead of a wait and watch approach, andmaximal safe resection not only changes the naturalhistory of the disease but also improves overall survival aswell as malignant progression free survival. Supratotalresection is a promising concept and has shown toVol. 67, No. 6, June 2017Extent of resection and timing of surgery in adult low grade glioma 960Figure: a) MRI T2WI of a left frontal low grade glioma. b) Post op MRI T2WI of samepatient showing more than 90% resection after awake craniotomy.significantly improve outcomes. The heterogeneity ofpatient population, presenting symptoms, involvement ofeloquent areas, and availability of local surgical resourcesto deal with these lesions in an effective fashion maybelimited in a developing or third world nation.References1. Smith DF, Hutton JL, Sandemann D, Foy PM, Shaw MD, Williams IR,et al. The prognosis of primary intracerebral tumours presentingwith epilepsy: the outcome of medical and surgical management.J Neurol Neurosurg Psychiatry. 1991; 54: 915-20.2. vanVeelen ML, Avezaat CJ, Kros JM, van Putten W, Vecht C.Supratentorial low grade astrocytoma: prognostic factors,dedifferentiation, and the issue of early versus late surgery. JNeurol Neurosurg Psychiatry. 1998; 64: 581-7.3. Jakola AS, Myrmel KS, Kloster R, Torp SH, Lindal S, Unsgård G, et al.Comparison of a strategy favoring early surgical resection vs astrategy favoring watchful waiting in low-grade gliomas. JAMA.2012; 308: 1881-8.4. Philippon JH, Clemenceau SH, Fauchon FH, Foncin JF.Supratentorial low-grade astrocytomas in adults. Neurosurgery.1993; 32: 554-9.5. Smith JS, Chang EF, Lamborn KR, Chang SM, Prados MD, Cha S, etal. Role of extent of resection in the long-term outcome of low-grade hemispheric gliomas. J Clin Oncol 2008; 26: 1338-45. 6. McGirt MJ, Chaichana KL, Attenello FJ, Weingart JD, Than K,Burger PC, et al. Extent of surgical resection is independentlyassociated with survival in patients with hemispheric infiltratinglow-grade gliomas. Neurosurgery. 2008; 63: 700-7; author reply707-8.7. Johannesen TB, Langmark F, Lote K. Progress in long-term survivalin adult patients with supratentorial low-grade gliomas: apopulation-based study of 993 patients in whom tumors werediagnosed between 1970 and 1993. J Neurosurg 2003; 99: 854-62.8. Hardesty DA, Sanai N. The value of glioma extent of resection inthe modern neurosurgical era. Front. Neur 2012; 3: 140. 9. Yordanova YN, Moritz-Gasser S, Duffau H. Awake surgery for WHOGrade II gliomas within "noneloquent" areas in the left dominanthemisphere: toward a "supratotal" resection. Clinical article. JNeurosurg 2011; 115: 232-9.J Pak Med Assoc961 F. A. Mirza, M. S. Shamim

Extent of resection and timing of surgery in adult low grade glioma

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Extent of resection and timing of surgery in adult low grade glioma

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