Prognostic Value of Brain/Cerebellum to Liver 18F-FDG Uptake Ratios in Lymphoid Malignancies

Overview

Ratios of brain or cerebellum to liver 18F-FDG uptake on PET/CT have been shown to stratify prognosis in multiple myeloma and various lymphomas. Lower ratios correlate with inferior progression-free and overall survival, supporting their potential as prognostic biomarkers.

Background

Tumor metabolic activity can compete with brain glucose uptake, affecting 18F-FDG PET imaging metrics. Prior studies demonstrated this phenomenon in non-Hodgkin lymphomas, leading to the development of the cerebellum/liver index for prognosis (CLIP). CLIP uses SUVmax of the cerebellum normalized to liver uptake to predict outcomes in lymphoid malignancies, addressing limitations of whole brain measurements and neurodegenerative confounders.

Data Highlights

Key Findings

• Brain/liver 18F-FDG uptake ratio <2.5 is associated with worse survival in multiple myeloma patients undergoing CAR T-cell therapy.
• CLIP, using cerebellum SUVmax normalized to liver uptake, predicts progression-free and overall survival in various lymphomas.
• Optimal prognostic thresholds for brain/cerebellum to liver ratios range between 2 and 4 across studies.
• Continuous modeling of CLIP values may provide better prognostic information than dichotomous cut-offs.
• Potential confounders include age-related neurodegeneration and glycemia, though their impact appears limited.
• Further research is needed to integrate these ratios with established prognostic indices.

Clinical Implications

Measuring cerebellum to liver 18F-FDG uptake ratios on PET/CT can aid risk stratification in lymphoid malignancies and multiple myeloma. Using SUVmax of the cerebellum enhances reproducibility, and continuous variable analysis may improve prognostic accuracy. Clinicians should consider potential confounders such as patient age and glycemia when interpreting these ratios.

Conclusion

Brain or cerebellum to liver 18F-FDG uptake ratios represent promising prognostic biomarkers in hematologic malignancies, with consistent associations to survival outcomes. Ongoing studies will clarify their role alongside existing prognostic tools.

References

1. Dingli et al. 2023 -- Brain to liver 18F-FDG uptake ratio predicts survival in multiple myeloma
2. Hanaoka et al. 2010 -- Tumor glucose metabolism competes with brain uptake in non-Hodgkin lymphoma
3. Author et al. 2021 -- CLIP as a prognostic factor in lymphomas
4. Author et al. 2022 -- CLIP in follicular lymphoma
5. Author et al. 2023 -- CLIP in Post-Transplant Lymphoproliferative Disorders
6. Author et al. 2021 -- Metabolic tumor volume and cerebellar uptake in Hodgkin lymphoma
7. Murairi et al. 2023 -- Continuous modeling of CLIP in diffuse large B-cell lymphoma