Interim FDG-PET improves treatment failure prediction in primary central nervous system Lymphoma: a LOC network prospective multicentric study.

in Neuro-oncology by Laura Rozenblum, Caroline Houillier, Amandine Baptiste, Carole Soussain, Véronique Edeline, Philippe Naggara, Marine Soret, Valérie Causse-Lemercier, Lise Willems, Sylvain Choquet, Renata Ursu, Damien Galanaud, Lisa Belin, Khê Hoang-Xuan, Aurélie Kas

TLDR

  • The study found that FDG-PET response at interim predicted patient outcomes, and highlights the potential of interim FDG-PET for early management of PCNSL patients.

Abstract

The purpose of our study was to assess the predictive and prognostic role of 2-18F-fluoro-2-deoxy-D-glucose (FDG) PET/MRI during high-dose methotrexate-based chemotherapy (HD-MBC) in de novo primary central nervous system lymphoma (PCNSL) patients aged 60 and above. This prospective multicentric ancillary study included 65 immunocompetents patients who received induction HD-MBC as part of the BLOCAGE01 phase III trial. FDG-PET/MRI were acquired at baseline, post two cycles (PET/MRI2), and post-treatment (PET/MRI3). FDG-PET response was dichotomized, with "positive" indicating persistent tumor uptake higher than the contralateral mirroring brain region. Performances of FDG-PET and International PCNSL Collaborative Group criteria in predicting induction response, progression-free survival (PFS), and overall survival (OS) were compared. Of 48 PET2 scans performed, nine were positive and aligned with a partial response (PR) on MRI2. Among these, eight (89%) progressed by the end of the induction phase. In contrast, 35/39 (90%) of PET2-negative patients achieved complete response (CR). Among the 18 discordant responses at interim (PETCR/MRIPR), 83% ultimately achieved CR. 87% of the PET2-negative patients were disease-free at 6 months versus 11% of the PET2-positive patients (p<0.001). The MRI2 response did not significantly differentiate patients based on their PFS, regardless of whether they were in CR or PR. Both PET2 and MRI2 independently predicted OS in multivariate analysis, with PET2 showing stronger association. Our study highlights the potential of interim FDG-PET for early management of PCNSL patients. Response-driven treatment based on PET2 may guide future clinical trials.

Overview

  • The study aimed to investigate the predictive and prognostic role of 2-18F-fluoro-2-deoxy-D-glucose (FDG) PET/MRI during high-dose methotrexate-based chemotherapy (HD-MBC) in de novo primary central nervous system lymphoma (PCNSL) patients aged 60 and above.
  • The study used a prospective multicentric ancillary design, including 65 immunocompetent patients who received induction HD-MBC as part of the BLOCAGE01 phase III trial.
  • The primary objective was to compare the performances of FDG-PET and International PCNSL Collaborative Group criteria in predicting induction response, progression-free survival (PFS), and overall survival (OS)

Comparative Analysis & Findings

  • The study found that FDG-PET response at interim (PET2) was a strong predictor of PFS, with 87% of PET2-negative patients being disease-free at 6 months compared to 11% of PET2-positive patients (p<0.001).
  • MRI2 response did not significantly differentiate patients based on their PFS, regardless of whether they were in complete response (CR) or partial response (PR).
  • Both PET2 and MRI2 independently predicted OS in multivariate analysis, with PET2 showing a stronger association

Implications and Future Directions

  • The study highlights the potential of interim FDG-PET for early management of PCNSL patients, enabling response-driven treatment and guiding future clinical trials
  • Future studies should investigate the optimal timing of FDG-PET imaging and its integration with other biomarkers to improve treatment outcomes
  • The development of response-driven treatment strategies based on FDG-PET imaging may improve patient outcomes and reduce treatment-related toxicity
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