Opinion statement
Low grade gliomas (LGG) encompass primary brain tumors that are typically well-differentiated and do not exhibit frankly malignant histologic features. These tumors can be further classified by their cellular morphology (eg, oligodendroglioma, pilocytic astrocytoma, etc), which does convey prognostic and therapeutic implications. Typically, low grade gliomas convey an overall better prognosis for patients as opposed to the higher grade primary brain tumors. Surgery for low grade gliomas and timing of such intervention remains controversial. Maximal resection of these tumors appears to prolong progression free survival. Advanced surgical techniques, including language mapping and awake craniotomies, have been shown to decrease morbidity associated with resection of lesions in eloquent areas of the brain. Radiation therapy has been proven effective in increasing time to progression in LGG, and emerging data support a role for combined modality therapy incorporating chemotherapy. Postoperative RT has been shown to have significant benefits with regards to progression free survival. Recent advances in molecular genetic markers, including the combined loss of chromosome arms 1p and 19q, and the mutation of the isocitrate dehydrogenase gene (IDH1/IDH2) have allowed for increased accuracy of predicting susceptibility to chemotherapeutic agents, as well as having some role in determining prognosis. PCV and temozolomide chemotherapy have both been studied when assessing progression free survival for LGG patients. Approaching patients with LGGs can be somewhat daunting given the lack of Class I evidence based protocols. However, significant evidence is now mounting to suggest early, maximal surgical excision; followed by fractionated RT will be the mainstays of treatment. Clearly, additional evidence is also mounting for the addition of chemotherapy in the treatment paradigm for patients with LGGs.
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References
Papers of particular interest, published recently, have been highlighted as:• Of importance
Wallner KE, Gonzales MF, Edwards MS, Wara WM, Sheline GE. Treatment results of juvenile pilocytic astrocytoma. J Neurosurg. 1988;69:171–6.
Ostrom QT, Gittleman H, Farah P, Ondracek A, Chen Y, Wolinsky Y, et al. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2006-2010. Neuro Oncol. 2013;15. This report summarizes all epidemiologic data concerning newly diagnosed LGG in the United States between 2006-2010.
Pallud JE, Audureau M, Blonski N, Sanai L, Bauchet D, Fontaine E, et al. Epileptic seizures in diffuse low-grade gliomas in adults. Brain. 2014;137:449–62.
Sahin N, Melhem ER, Wang S, Krejza J, Poptani H, Chawla S, et al. Advanced MR imaging techniques in the evaluation of nonenhancing gliomas: perfusion-weighted imaging compared with proton magnetic resonance spectroscopy and tumor grade. Neuroradiol J. 2013;26:531–41.
Karim AB, Afra D, Cornu P, Bleehan N, Schraub S, De Witte O, et al. Randomized trial on the efficacy of radiotherapy for cerebral low-grade glioma in the adult: European Organization for Research and Treatment of Cancer Study 22845 with the Medical Research Council study BRO4: an interim analysis. Int J Radiat Oncol Biol Phys. 2002;52:316–24.
van den Bent MJ, Afra D, de Witte O, Ben Hassel M, Schraub S, Hoang K, et al. Long-term efficacy of early vs delayed radiotherapy for low-grade astrocytoma and oligodendroglioma in adults: the EORTC 22845 randomised trial. Lancet. 2005;366:985–90.
Pignatti FM, van den Bent D, Curran C, Debruyne R, Sylvester R, Therasse P, et al. Prognostic factors for survival in adult patients with cerebral low-grade glioma. J Clin Oncol. 2002;20:2076–84.
Daniels TB, Brown D, Felten SJ, Wu W, Buckner JC, Arusell RM, et al. Validation of EORTC prognostic factors for adults with low-grade glioma: a report using intergroup 86-72-51. Int J Radiat Oncol Biol Phys. 2011;81:218–24. This inter-group analysis confirmed independent prognostic factors with regards to prognosis for LGG patients).
Jenkins RB, Blair H, Ballman KV, Giannini C, Arusell RM, Law MA. t(1;19)(q10;p10) mediates the combined deletions of 1p and 19q and predicts a better prognosis of patients with oligodendroglioma. Cancer Res. 2006;66:9852–61.
Houillier CX, Wang G, Kaloshi K, Mokhtari R, Guillevin J, Laffaire S, et al. IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas. Neurology. 2010;75:1560–6.
Yan HD, Parsons W, Jin G, McLendon R, Rasheed BA, Yuan W, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med. 2009;360:765–73.
Pouratian N, Asthagiri A, Jagannathan J, Shaffrey ME, Schiff D. Surgery insight: the role of surgery in the management of low-grade gliomas. Nat Clin Pract Neurol. 2007;3:628–39.
Jakola AS, Myrmel KS, Kloster R, Torp SH, Lindal S, Unsgard G, et al. Comparison of a strategy favoring early surgical resection vs a strategy favoring watchful waiting in low-grade gliomas. JAMA. 2012;308:1881–8. This study confirmed the benefit of early surgical resection of LGG rather than watchful waiting.
Sanai N, Berger MS. Glioma extent of resection and its impact on patient outcome. Neurosurgery. 2008;62:753–64.
Sanai N, Berger MS. Extent of resection influences outcomes for patients with gliomas. Rev Neurol. 2011;167:648–54.
Smith JS, Chang EF, Lamborn KR, Chang SM, Prados MD, Cha S, et al. Role of extent of resection in the long-term outcome of low-grade hemispheric gliomas. J Clin Oncol. 2008;26:1338–45.
Chang EF, Potts MB, Keles GE, Lamborn KR, Chang SM, Barbaro NM. Seizure characteristics and control following resection in 332 patients with low-grade gliomas. J Neurosurg. 2008;108:227–35.
Soffietti RB, Baumert G, Bello L, von Deimling A, Duffau H, Frenay M, et al. Guidelines on management of low-grade gliomas: report of an EFNS-EANO Task Force. Eur J Neurol. 2010;17:1124–33.
Sanai N, Berger MS. Intraoperative stimulation techniques for functional pathway preservation and glioma resection. Neurosurg Focus. 2010;28:E1.
Sanai N, Berger MS. Operative techniques for gliomas and the value of extent of resection. Neurotherapeutics. 2009;6:478–86.
Taylor MD, Bernstein M. Awake craniotomy with brain mapping as the routine surgical approach to treating patients with supratentorial intra-axial tumors: a prospective trial of 200 cases. J Neurosurg. 1999;90:35–41.
Claus EB, Horlacher A, Hsu L, Schwartz RB, Dello-Iacono D, Talos F, et al. Survival rates in patients with low-grade glioma after intraoperative magnetic resonance image guidance. Cancer. 2005;103:1227–33.
Pamir MN, Ozduman K, Dincer A, Yildiz E, Peker S, Ozek MM. First intraoperative, shared-resource, ultrahigh-field 3-Tesla magnetic resonance imaging system and its application in low-grade glioma resection. J Neurosurg. 2010;112:57–69.
Karim AB, Maat B, Hatlevoll R, Menten J, Rutten EH, Thomas DG, et al. A randomized trial on dose-response in radiation therapy of low-grade cerebral glioma. European Organization for Research and Treatment of Cancer (EORTC) Study 22844. Int J Radiat Oncol Biol Phys. 1996;36:549–56.
Brown D, Buckner JC, O'Fallon JR, Iturria NL, Brown CA, O'Neill BP, et al. Effects of radiotherapy on cognitive function in patients with low-grade glioma measured by the Folstein Mini-Mental State examination. J Clin Oncol. 2003;21:2519–24.
Surma-aho O, Niemela M, Vilkki J, Kouri M, Brander A, Salonen O, et al. Adverse long-term effects of brain radiotherapy in adult low-grade glioma patients. Neurology. 2001;56:1285–90.
Douw L, Klein M, Fagel SS, van den Heuvel J, Taphoorn MJ, Aaronson NK, et al. Cognitive and radiological effects of radiotherapy in patients with low-grade glioma: long-term follow-up. Lancet Neurol. 2009;8:810–8.
Baumert B. Temozolomide chemotherapy vs radiotherapy in molecularly characterized (1p loss) low-grade glioma: a randomized phase III intergroup study by the EORTC/NCIC-CTG/TROG/MRC-CTU (EORTC 22033-26033). Oral abstract session at American Society of Clinical Oncology annual meeting. 2013.
Fisher BJ. A phase II study of a temozolomide-based chemoradiotherapy regimen for high-risk low-grade gliomas: preliminary results of RTOG 0424. Oral abstract session at American Society of Clinical Oncology annual meeting. 2013.
Shaw EG, Wang M, Coons SW, Brachman DG, Buckner JC, Stelzer KJ, et al. Randomized trial of radiation therapy plus procarbazine, lomustine, and vincristine chemotherapy for supratentorial adult low-grade glioma: initial results of RTOG 9802. J Clin Oncol. 2012;30:3065–70.
Buckner J. Phase III study of radiation therapy (RT) with or without procarbazine, CCNU, and vincristine (PCV) in low-grade glioma: RTOG 9802 with Alliance, ECOG, and SWOG. Oral abstract session at American Society of Clinical Oncology annual meeting. 2014.
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Conflict of InterestAdesh Tandon declares that he has no conflicts of interest. David Schiff has served on an advisory board for Sigma Tau.
Human and Animal Rights and Informed ConsentThis article does not contain any studies with human or animal subjects performed by any of the authors.
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All of the listed authors have made substantial contributions in the conception and design of this short report. They have all, also participated in the acquisition and analysis of the data. All of the authors made contributions in drafting this journal submission and approved its final draft for submission.
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Tandon, A., Schiff, D. Therapeutic Decision Making in Patients with Newly Diagnosed Low Grade Glioma. Curr. Treat. Options in Oncol. 15, 529–538 (2014). https://doi.org/10.1007/s11864-014-0304-6
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DOI: https://doi.org/10.1007/s11864-014-0304-6