Recurrence following neurosurgeon-determined gross-total resection of adult supratentorial low-grade glioma: results of a prospective clinical trial

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In 1998, the Radiation Therapy Oncology Group initiated a Phase II study of observation for adults < 40 years old with cerebral low-grade glioma who underwent a neurosurgeon-determined gross-total resection (GTR).


Patient eligibility criteria included the presence of a World Health Organization Grade II astrocytoma, oligodendroglioma, or mixed oligoastrocytoma confirmed histologically; age 18–39 years; Karnofsky Performance Scale score ≥ 60; Neurologic Function Scale score ≤ 3; supratentorial tumor location; neurosurgeon-determined GTR; and pre- and postoperative MR imaging with contrast enhancement available for central review by the principal investigator. Patients were observed following GTR and underwent MR imaging every 6 months. Prognostic factors analyzed for their contribution to patient overall survival, progression-free survival (PFS), and tumor recurrence included age, sex, Karnofsky Performance Scale score, Neurologic Function Scale score, histological type, contrast enhancement on preoperative MR imaging, preoperative tumor diameter, residual disease based on postoperative MR imaging, and baseline Mini-Mental State Examination score.


Between 1998 and 2002, 111 eligible patients were entered into the study. In these 111 patients, the overall survival rates at 2 and 5 years were 99 and 93%, respectively. The PFS rates in these 111 patients at 2 and 5 years were 82 and 48%, respectively. Three prognostic factors predicted significantly poorer PFS in univariate and multivariate analyses: 1) preoperative tumor diameter ≥ 4 cm; 2) astrocytoma/oligoastrocytoma histological type; and 3) residual tumor ≥ 1 cm according to MR imaging. Review of the postoperative MR imaging results revealed that 59% of patients had < 1 cm residual disease (with a subsequent 26% recurrence rate), 32% had 1–2 cm residual disease (with a subsequent 68% recurrence rate), and 9% had > 2 cm residual disease (with a subsequent 89% recurrence rate).


These data suggest that young adult patients with low-grade glioma who undergo a neurosurgeondetermined GTR have a > 50% risk of tumor progression 5-years postoperatively, warranting close follow-up and consideration for adjuvant treatment.

Abbreviations used in this paper: CI = confidence interval; EORTC = European Organization for the Research and Treatment of Cancer; GTR = gross-total resection; HR = hazard ratio; KPS = Karnofsky Performance Scale; LGG = low-grade glioma; MMSE = Mini-Mental State Examination; NCCTG = North Central Cancer Treatment Group; NFS = Neurological Function Scale; OS = overall survival; PCV = procarbazine, CCNU, and vincristine; PFS = progression-free survival; RTOG = Radiation Therapy Oncology Group; STR = subtotal resection; WHO = World Health Organization.

Article Information

Address correspondence to: Edward G. Shaw, M.D., Department of Radiation Oncology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157. email:

© AANS, except where prohibited by US copyright law.



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    Preoperative (A and C) and postoperative (B and D) MR images of patients who underwent a neurosurgeon-determined GTR and were found to have < 1 cm of imaging-based residual disease (A and B) or 1–2 cm residual disease (C and D).

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    Line graph showing the overall survival and PFS curves for the 111 patients with favorable (low risk) LGG and the 251 patients with unfavorable (high risk) LGG.

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    Line graph showing patient PFS according to 2 different tumor diameters (< 4 cm vs ≥ 4 cm).

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    Line graph showing patient PFS according to histological type (pure oligodendroglioma vs astrocytoma and mixed oligoastrocytoma).

  • View in gallery

    Line graph of patient PFS according to surgical residual tumor (< 1 cm vs ≥ 1 cm).

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    Line graph showing patient PFS according to 3 different prognostic factor groups: the favorable group (< 1 cm residual tumor, tumor diameter < 4 cm, and oligodendroglioma histological type); the unfavorable group (≥ 1 cm residual tumor according to imaging, preoperative tumor diameter ≥ 4 cm, and astrocytoma histological type); and the group of patients with tumors with a mix of favorable and unfavorable characteristics.



Berger MSDeliganis AVDobbins JKeles GE: The effect of extent of resection on recurrence in patients with low grade cerebral hemispheric gliomas. Cancer 72:178417911994


Berger MSRostomily RC: Low grade gliomas: functional mapping resection strategies, extent of resection, and outcome. J Neurooncol 34:851011997


Brown PDBuckner JCO'Fallon JRIturria NLBrown CAO'Neill BP: Adult Patients with Supratentorial Pilocytic Astrocytomas: a prospective multicenter clinical trial. Int J Radiat Oncol Biol Phys 58:115311602004


Brown PDShaw EGLow-Grade Gliomas. Gunderson LLTepper JE: Clinical Radiation Oncology ed 2PhiladelphiaChurchill-Livingstone2006. 493514


Bynevelt MBritton JSeymour HMacSweeney EThomas NSandhu K: FLAIR imaging in the follow-up of low-grade gliomas: time to dispense with the dual-echo?. Neuroradiology 43:1291332001


Central Brain Tumor Registry of the United States: United StatesCBRTUS2005


Chang SMParney IFHuang WAnderson FA JrAsher ALBernstein M: Patterns of care for adults with newly diagnosed malignant glioma. JAMA 293:5575642005


Claus EBHorlacher AHsu LSchwartz RBDello-Iacono DTalos F: Survival rates in patients with low-grade glioma after intraoperative magnetic resonance image guidance. Cancer 103:122712332005


Hayostek CShaw EScheithauer BO'Fallon JrWeiland TLSchomberg PJ: Astrocytomas of the cerebellum. A comparative clinicopathologic study of pilocytic and diffuse astrocytomas. Cancer 72:8568591993


Jemal ASiegel RWard EMurray TXu JSmigal C: Cancer Statistics, 2006. CA Cancer J Clin 56:1061302006


Jenkins RBBlair HBallman KVGiannini CArusell RMLaw M: A t(1;19)(q10;p10) mediates the combined deletions of 1p and 19q and predicts a better prognosis of patients with oligodendroglioma. Cancer Res 66:985298612006


Karim ABAfra DCornu PBleehan NSchraub SDeWitte O: 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 BR04: an Interim Analysis. Int J Radiat Oncol Biol Phys 52:3163242002


Karim ABMaat BHatlevoll RMenten JRutten EHThomas DG: A randomized trial on dose-response in radiation therapy of low-grade cerebral glioma: European Organization for Research and Treatment of Cancer Study (EORTC) Study 22844. Int J Radiat Oncol Biol Phys 36:5495561996


Kleihues PBurger PCScheithauer BW: Histological Typing of Tumours of the Central Nervous System ed 2BerlinSpringer1993


Minehan KJShaw EGScheithauer BWDavis DLOnofrio BM: Spinal cord astrocytoma: pathologic and treatment considerations. J Neurosurg 83:5905951995


Nimsky CGanslandt OHastreiter PWang RBenner TSorensen AG: Preoperative and intraoperative diffusion tensor imaging-based fiber tracking in glioma surgery. Neurosurgery 56:1301372005


Nimsky CGanslandt Ovon Keller BFahlbusch R: Intraoperative high-field MRI: anatomical and functional imaging. Acta Neurochir Suppl 9887952006


Pallud JDevaux BNataf FRoux FXDaumas-Duport C: Spatial delimitation of low grade oligodendrogliomas. Neurochirurgie 51:2542592005


Pirzkall ANelson SJMcKnight TRTakahashi MMLi XGraves EE: Metabolic imaging of low-grade gliomas with three-dimensional magnetic resonance spectroscopy. Int J Radiat Oncol Biol Phys 53:125412642002


Schmidt MHBerger MSLamborn KRAldape KMcDermott MWPrados MD: Repeated operations for infiltrative low-grade gliomas without intervening therapy. J Neurosurg 98:116511692003


Shaw EArusell RScheithauer BO'Fallon JO'Neill BDinapoli R: A prospective randomized trial of low- versus high-dose radiation therapy in adults with supratentorial low-grade glioma: initial report of a NCCTG-RTOG-ECOG study. J Clin Oncol 20:226722762002


Shaw EGScheithauer BWGilbertson DTNichols DALaws EREarle JD: Postoperative radiotherapy of supratentorial low-grade gliomas. Int J Radiat Oncol Biol Phys 16:6636681989


Stummer WPichlmeier UMeinel TWiestler ODZanella FReulen HJ: Flourescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol 7:392 4012006


Talos IFZou KHOhno-Machado LBhagwat JGKikinis RBlack PM: Supratentorial low-grade glioma resectability: statistical predictive analysis based on anatomic MR features and tumor characteristics. Radiology 239:5065132006


van den Bent MJAfra Dde Witte OBen Hassel MSchraub SHoang-Xuan K: Long-term efficacy of early versus delayed radiotherapy for low-grade astrocytoma and oligodendroglioma in adults: the EORTC 22845 randomised trial. Lancet 366:9859902005


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