Long-term treatment outcomes of temozolomide-based chemoradiation in patients with adult-type diffuse IDH-mutant grade 2 astrocytoma

J Neurooncol. 2023 Sep;164(2):331-339. doi: 10.1007/s11060-023-04418-z. Epub 2023 Sep 4.

Abstract

Purpose: To report the long-term outcomes in adult patients with grade 2 IDH-mutant astrocytoma treated with temozolomide (TMZ)-based chemoradiation.

Methods: One hundred and three patients with histologically proven grade 2 astrocytoma received radiation therapy (RT), 50.4-54 Gy in 1.8 Gy fractions, and adjuvant TMZ up to 12 cycles. Fifty-two patients received RT at the time of tumor progression and 51 in the early postoperative period for the presence of at least one high-risk feature (age > 40 years, preoperative tumor size > 5 cm, large postoperative residual tumor, tumor crossing the midline, or presence of neurological symptoms). Overall survival (OS) and progression-free survival (PFS) were calculated from the time of diagnosis.

Results: With a median follow-up time of 9.0 years (range, 1.3-15 years), median PFS and OS times were 9 years (95%CI, 6.6-10.3) and 11.8 years (95%CI, 9.3-13.4), respectively. Median PFS was 10.6 years in the early treatment group and 6 years in delayed treatment group (hazard ratio (HR) 0.30; 95%CI 0.16-0.59; p = 0.0005); however, OS was not significantly different between groups (12.8 vs. 10.4 years; HR 0.64; 95%CI 0.33-1.25; p = 0.23). Extent of resection, KPS, and small residual disease were associated with OS, with postoperative tumor ≤ 1 cc that emerged as the strongest independent predictor (HR: 0.27; 95%CI 0.08-0.87; p = 0.01).

Conclusions: TMZ-based chemoradiation is associated with survival benefit in patients with grade 2 IDH-mutant astrocytoma. For this group of patients, chemoradiation can be deferred until time of progression in younger patients receiving extensive resection, while early treatment should be recommended in high-risk patients.

Keywords: Grade 2 astrocytoma; IDH-mutant adult diffuse glioma; Molecular markers; Radiotherapy; Temozolomide.

MeSH terms

  • Adult
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Astrocytoma* / genetics
  • Astrocytoma* / pathology
  • Astrocytoma* / therapy
  • Brain Neoplasms* / diagnosis
  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / therapy
  • Dacarbazine / therapeutic use
  • Humans
  • Temozolomide / therapeutic use
  • Treatment Outcome

Substances

  • Temozolomide
  • Antineoplastic Agents, Alkylating
  • Dacarbazine