Is IDH status the only factor predicting prognosis in newly diagnosed anaplastic glioma patients? Outcome evaluation and prognostic factor analysis in a single-institution large series

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  • 1 Departments of Radiotherapy and Radiosurgery,
  • | 2 Neurosurgery,
  • | 3 Oncology and Hematology, and
  • | 4 Neuroradiology, Humanitas Cancer Center and Research Hospital, Rozzano;
  • | 5 Department of Biomedical Sciences, Humanitas University, Rozzano; and
  • | 6 Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Italy
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OBJECTIVE

Anaplastic gliomas (AGs) are an extremely heterogeneous group of primary brain tumors. More recently, new discoveries have indicated that isocitrate dehydrogenase (IDH) mutation status is the most important parameter predicting survival. The primary aim of the present analysis was to identify prognostic factors, other than IDH status, that eventually impact survival.

METHODS

Patients with available clinical, imaging, and molecular profile data who were amenable to resection were evaluated. The extent of resection (EOR) was defined as gross-total resection (GTR), near-total resection (NTR), subtotal resection (STR), or partial resection (PR). Residual tumor volume (RTV) was quantified. Following surgery, patients received adjuvant chemotherapy alone, radiation therapy plus concomitant and adjuvant temozolomide (TMZ), or sequential radio-chemotherapy. Clinical outcome was evaluated by neurological examination and MRI 1 month after treatment and every 4 months thereafter. Tumor progression was defined according to the Response Assessment in Neuro-Oncology (RANO) working group.

RESULTS

Among 402 patients referred to the authors’ institution for AG, 142 were included in the present analysis. Eighty-eight (62%) were male and 54 (38%) were female, with a median age of 43 years (range 19–70 years). At admission, most patients had a Karnofsky Performance Scale score of 90–100 (84.5%) and were symptomatic (93.7%). Forty-eight (33.8%) patients had newly diagnosed anaplastic oligodendrogliomas (AOs), and 94 (66.2%) had anaplastic astrocytomas (AAs). Most of them had mutant IDH tumors (67.6%) and methylated O 6-methylguanine-DNA-methyltransferase (MGMT) promoter status (71.8%). GTR was performed in more than half of the patients (56.3%). RTV was detected in 83 (58.5%) patients. Following surgery, 72 (50.7%) patients received radiotherapy with concomitant and adjuvant TMZ, 48 (33.8%) received sequential radio-chemotherapy, and 22 (15.5%) received adjuvant chemotherapy alone. The median follow-up time was 40 months (range 16–146 months). The median PFS time and the 1-, 3-, and 5-year PFS rates were 35 months (95% CI 27–76) and 78.9% ± 3.4%, 49.7% ± 4.6%, and 42.7% ± 5.4%, respectively. The median OS time and the 1-, 3-, and 5-year OS rates were 91 months (95% CI 66–95) and 90.1% ± 2.5%, 70.9% ± 4.2%, and 61.8% ± 4.9%, respectively. Prognostic factors predicting survival other than molecular profile were the EOR and the RTV (p < 0.0001). Sequential radio-chemotherapy was the more effective treatment administered.

CONCLUSIONS

In addition to IDH status, EOR and the RTV have proved to statistically impact survival. The pivotal role of adjuvant radiotherapy has been recorded in all AG patients, regardless of tumor features.

ABBREVIATIONS

AA = anaplastic astrocytoma; AG = anaplastic glioma; AO = anaplastic oligodendroglioma; AOA = anaplastic oligoastrocytoma; CE = contrast-enhanced; EOR = extent of resection; EORTC = European Organisation for Research and Treatment of Cancer; GBM = glioblastoma; GTR = gross-total resection; IDH = isocitrate dehydrogenase; KPS = Karnofsky Performance Scale; MGMT = O 6-methylguanine-DNA-methyltransferase; NR = not reached; NTR = near-total resection; OS = overall survival; PCV = procarbazine, lomustine, and vincristine; PFS = progression-free survival; PR = partial resection; RTOG = Radiation Therapy Oncology Group; RTV = residual tumor volume; STR = subtotal resection; TMZ = temozolomide.
Illustrations from Marx and Schroeder (pp 318–326). Copyright Henry W. S. Schroeder. Published with permission.

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Contributor Notes

Correspondence Federico Pessina: Humanitas Cancer Center and Research Hospital, Rozzano, Italy. federico.pessina@hunimed.eu.

INCLUDE WHEN CITING Published online September 4, 2020; DOI: 10.3171/2020.5.JNS201116.

Disclosures Dr. Santoro: consultant for Arqule and Sanofi; speakers bureau for Takeda, BMS, Roche, AbbVie, Amgen, Celgene, Servier, Gilead, AstraZeneca, Pfizer, Arqule, Lilly, Sandoz, Eisai, Novartis, Bayer, and MSD; and advisory board for BMS, Servier, Gilead, Pfizer, Eisai, Bayer, and MSD.

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