Final Results of the Prospective Biomarker Trial PETra: [11C]-MET-Accumulation in Postoperative PET/MRI Predicts Outcome after Radiochemotherapy in Glioblastoma

Clin Cancer Res. 2021 Mar 1;27(5):1351-1360. doi: 10.1158/1078-0432.CCR-20-1775. Epub 2020 Dec 29.

Abstract

Purpose: This prospective trial investigates the association of time to recurrence (TTR) in glioblastoma with [11C]methionine (MET) tracer uptake before postoperative radiochemotherapy (RCT) aiming to guide radiotherapy boost regions.

Experimental design: Between 2013 and 2016, 102 patients with glioblastoma were recruited. RCT was performed with concurrent and adjuvant temozolomide to a total dose of 60 Gy. Tumor residues in postresection PET and MRI were together defined as gross tumor volumes for radiotherapy treatment planning. [11C]methionine (MET)-PET/MRI was performed before RCT and at each follow-up.

Results: The primary hypothesis of a longer TTR for patients without increased tracer accumulation in postoperative MET-PET was confirmed in 89 patients. With 18.9 months (95% confidence interval, 9.3-28.5 months), median TTR was significantly (P < 0.001) longer for patients without (n = 29, 32.6%) as compared with 6.3 months (3.6-8.9) for patients with MET accumulation (n = 60, 67.4%) in pre-RCT PET. Although MRI often did not detect all PET-positive regions, an unfavorable impact of residual tumor in postsurgical MRI (n = 38, 42.7%) on TTR was observed [4.6 (4.2-5.1) vs. 15.5 months (6.0-24.9), P < 0.001]. Significant multivariable predictors for TTR were MRI positivity, PET-positive volume, and O6-methylguanine DNA methyltransferase (MGMT) hypermethylation.

Conclusions: Postsurgical amino acid PET has prognostic value for TTR after RCT in glioblastoma. Because of the added value of the metabolic beyond the pure structural information, it should complement MRI in radiotherapy planning if available with reasonable effort, at least in the context of maximal therapy. Furthermore, the spatial correlation of regions of recurrence with PET-positive volumes could provide a bioimaging basis for further trials, for example, testing local radiation dose escalation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Biomarkers, Tumor / metabolism
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy
  • Carbon Radioisotopes / analysis
  • Carbon Radioisotopes / metabolism
  • Chemoradiotherapy / methods*
  • Combined Modality Therapy
  • DNA Methylation
  • DNA Modification Methylases / genetics
  • DNA Repair Enzymes / genetics
  • Female
  • Follow-Up Studies
  • Glioblastoma / diagnostic imaging
  • Glioblastoma / metabolism
  • Glioblastoma / pathology*
  • Glioblastoma / therapy
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Male
  • Methionine / metabolism*
  • Middle Aged
  • Neoplasm Recurrence, Local / diagnostic imaging
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / therapy
  • Positron-Emission Tomography / methods*
  • Postoperative Care*
  • Prognosis
  • Prospective Studies
  • Radiopharmaceuticals / metabolism*
  • Survival Rate
  • Temozolomide / therapeutic use
  • Tumor Suppressor Proteins / genetics
  • Young Adult

Substances

  • Antineoplastic Agents, Alkylating
  • Biomarkers, Tumor
  • Carbon Radioisotopes
  • Radiopharmaceuticals
  • Tumor Suppressor Proteins
  • Methionine
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes
  • Temozolomide