A Comparative Study of [18f]FDG PET and MRI for Evaluating Treatment Response in Primary CNS Lymphoma Patients Undergoing High-Dose Methotrexate Therapy
Authors: Oh Minyoung , Cho Hyungwoo , Park Ji Eun , Kim Ho Sung , Go Heounjeong , Park Chan-Sik , Lee Sang-wook , Song Sang Woo , Kim Young-Hoon , Cho Young Hyun , Hong Seok Ho , Kim Jeong Hoon , Lee Dong Yun , Ryu Jin-Sook , Yoon Dok Hyun , Kim Jae Seung 
Published: December 2024

Introduction :
The standard method for evaluating response in patients with primary central nervous system lymphoma (PCNSL) is T1-weighted contrast-enhanced brain magnetic resonance imaging (MRI). However, brain MRI has limitations in distinguishing between complete response (CR), radiologically unconfirmed complete response (CRu), and partial response (PR) when evaluating treatment responses to predict clinical outcomes. We have previously reported on the role of 18F-fluorodeoxyglucose brain positron emission tomography/computed tomography ([18F]FDG brain PET/CT) in prognostication and response evaluation of PCNSL (Oh and Cho et al, Neuro-oncology 2024). This study aims to prospectively validate the prognostic value of interim responses after two cycles of high-dose methotrexate-based chemotherapy and end-of-treatment responses using [18F]FDG brain PET/CT and MRI in patients with PCNSL undergoing first-line treatment.
Patients and m ethods:
From August 2021 to December 2023, 55 newly diagnosed PCNSL patients at Asan Medical Center in South Korea were prospectively enrolled, with ongoing enrollment aiming for a total of 90 patients. All patients received high-dose methotrexate-based chemotherapy as their first-line treatment and underwent [18F]FDG brain PET/CT alongside MRI for response evaluation. [18F]FDG brain PET/CT images were visually assessed as either negative (complete metabolic response: CMR) or positive (showing greater uptake than the contralateral brain or physiological uptake in midline structures) by two nuclear medicine physicians.
Results:
The median age of the 55 patients was 65 years (range: 28-84) with 26 male participants. With a median follow-up of 14 months (range: 3-33), nineteen patients experienced disease progression. Median progression-free survival (PFS) was not reached. The one-year PFS rate is 71.1% (95% confidence interval [CI]: 58.2% - 84.0%). During treatment, five patients dropped out before the prespecified interim evaluation and seven before the end-of-treatment evaluation due to disease progression, leaving 50 and 48 patients for interim and end-of-treatment response assessment, respectively. At the interim evaluation, MRI results showed 7 patients with CR, 43 with PR, and none with CRu or PD. There was no significant difference in PFS between patients who achieved a CR vs. those who achieved a PR, with a 1-year PFS rate of 51.4% (95% CI: 11.4% - 91.4%) vs. 78.3% (95% CI: 65.7% - 90.9%, p = 0.296). However, 24 patients (5 CR and 19 PR on MRI at the interim) demonstrated CMR on [18F]FDG brain PET/CT at the interim analysis. Of note, none of the patients who achieved CMR at interim PET/CT showed disease progression on MRI or PET/CT at the end of treatment response analysis. At the end-of-treatment evaluation, MRI results showed 27 patients with CR, 7 with CRu, 10 with PR, and 4 with PD. There were no statistical differences in predicting survival outcomes between CR, CRu, and PR on MRI at the end of treatment with a 1-year PFS rate of 87.7% (95% CI: 74.7% - 100.0%), 66.7% (95% CI: 29.1% - 100.0%) and 87.5%% (95% CI: 64.6% - 100.0%), respectively (p = 0.311). On the other hand, 44 patients showed CMR on [18F]FDG brain PET/CT at the end of treatment, which was associated with a better 1-year PFS (82.1% [95% CI: 70.1% vs. 94.1%] vs. 0.0% [95% CI was not calculable], p &lt; 0.001).
Conclusion :
In patients with PCNSL, response evaluation with MRI at the interim and end of treatment did not significantly differ in predicting survival outcomes. However, achieving CMR on [18F]FDG brain PET/CT at the end of treatment is associated with more favorable PFS. While interim PET shows potential as a prognostic indicator, further study is needed to establish its role. Our findings suggest a potential utility of [18F]FDG PET/CT in evaluating responses for patients with PCNSL. The results of the final analysis will be available upon completion of the study.