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

Clinical article

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Object

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).

Methods

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.

Results

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).

Conclusions

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: eshaw@wfubmc.edu.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    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).

  • View in gallery

    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.

  • View in gallery

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

  • View in gallery

    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).

  • View in gallery

    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.

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