To treat or not to treat? A retrospective multicenter assessment of survival in patients with IDH-mutant low-grade glioma based on adjuvant treatment

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  • 1 Department of Neurosurgery,
  • 6 Department of Pathology, Section of Neuropathology, and
  • 7 Department of Radiology, Section of Neuroradiology, University of Ulm, Günzburg;
  • 2 Department of Neurosurgery, University of Heidelberg;
  • 3 Department of Neurosurgery, University of Schleswig-Holstein, Kiel;
  • 4 Department of Neurosurgery, University of Tübingen; and
  • 5 Department of Neurosurgery, University of Frankfurt, Germany
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OBJECTIVE

The level of evidence for adjuvant treatment of diffuse WHO grade II glioma (low-grade glioma, LGG) is low. In so-called “high-risk” patients most centers currently apply an early aggressive adjuvant treatment after surgery. The aim of this assessment was to compare progression-free survival (PFS) and overall survival (OS) in patients receiving radiation therapy (RT) alone, chemotherapy (CT) alone, or a combined/consecutive RT+CT, with patients receiving no primary adjuvant treatment after surgery.

METHODS

Based on a retrospective multicenter cohort of 288 patients (≥ 18 years old) with diffuse WHO grade II gliomas, a subgroup analysis of patients with a confirmed isocitrate dehydrogenase (IDH) mutation was performed. The influence of primary adjuvant treatment after surgery on PFS and OS was assessed using Kaplan-Meier estimates and multivariate Cox regression models, including age (≥ 40 years), complete tumor resection (CTR), recurrent surgery, and astrocytoma versus oligodendroglioma.

RESULTS

One hundred forty-four patients matched the inclusion criteria. Forty patients (27.8%) received adjuvant treatment. The median follow-up duration was 6 years (95% confidence interval 4.8–6.3 years). The median overall PFS was 3.9 years and OS 16.1 years. PFS and OS were significantly longer without adjuvant treatment (p = 0.003). A significant difference in favor of no adjuvant therapy was observed even in high-risk patients (age ≥ 40 years or residual tumor, 3.9 vs 3.1 years, p = 0.025). In the multivariate model (controlled for age, CTR, oligodendroglial diagnosis, and recurrent surgery), patients who received no adjuvant therapy showed a significantly positive influence on PFS (p = 0.030) and OS (p = 0.009) compared to any other adjuvant treatment regimen. This effect was most pronounced if RT+CT was applied (p = 0.004, hazard ratio [HR] 2.7 for PFS, and p = 0.001, HR 20.2 for OS). CTR was independently associated with longer PFS (p = 0.019). Age ≥ 40 years, histopathological diagnosis, and recurrence did not achieve statistical significance.

CONCLUSIONS

In this series of IDH-mutated LGGs, adjuvant treatment with RT, CT with temozolomide (TMZ), or the combination of both showed no significant advantage in terms of PFS and OS. Even in high-risk patients, the authors observed a similar significantly negative impact of adjuvant treatment on PFS and OS. These results underscore the importance of a CTR in LGG. Whether patients ≥ 40 years old should receive adjuvant treatment despite a CTR should be a matter of debate. A potential tumor dedifferentiation by administration of early TMZ, RT, or RT+CT in IDH-mutated LGG should be considered. However, these data are limited by the retrospective study design and the potentially heterogeneous indication for adjuvant treatment.

ABBREVIATIONS −2LL = −2 log-likelihood; CI = confidence interval; CT = chemotherapy; CTR = complete tumor resection; EOR = extent of resection; EORTC = European Organization for Research and Treatment of Cancer; HR = hazard ratio; IDH = isocitrate dehydrogenase; iMRI = intraoperative MRI; KPS = Karnofsky Performance Scale; LGG = low-grade glioma; LOH = loss of heterogeneity; OS = overall survival; PCV = procarbazine, lomustine (CCNU), and vincristine; PFS = progression-free survival; RT = radiation therapy; RTOG = Radiation Therapy Oncology Group; STR = subtotal resection; TMZ = temozolomide.

Supplementary Materials

    • Supplemental Table 1 (PDF 389 KB)

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Contributor Notes

Correspondence Andrej Paľa: University of Ulm, Günzburg, Germany. andrej.pala@gmail.com.

INCLUDE WHEN CITING Published online July 19, 2019; DOI: 10.3171/2019.4.JNS183395.

A.P. and J.C. contributed equally to this work.

Disclosures Dr. Coburger reports being a consultant for BrainLAB.

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