The anatomical distribution of metabolic tumor burden provides prognostic information beyond whole-body ¹⁸F-FDG PET/CT metrics in de novo metastatic HER2-positive breast cancer.

OBJECTIVE

Whole-body PET metrics quantify the magnitude of metastatic burden but ignore its anatomical distribution. Whether resolving metabolic burden according to anatomical compartment provides incremental prognostic information beyond conventional whole-body PET metrics remains unknown. We therefore tested whether the anatomical distribution of metabolic burden carries prognostic information beyond aggregate whole-body load in de novo metastatic HER2-positive breast cancer.

METHODS

Fifty-seven consecutive treatment-naive patients who underwent baseline ¹⁸F-FDG PET/CT before first-line anti-HER2 therapy were retrospectively analyzed. Compartment-specific metabolic parameters and clinical variables were evaluated using multivariable Cox regression. Model discrimination was internally validated over 1000 bootstrap resamples, and the incremental value of compartment-specific burden over whole-body metrics was evaluated with likelihood-ratio tests.

RESULTS

Twenty patients (35.1%) died during a median follow-up of 50.4 months. LN_MTV, Bone_TLG, and HR status independently predicted OS, yielding a model with a modest optimism-corrected C-index of 0.685 when the entire variable-selection sequence was repeated within each bootstrap resample. Adding compartment-specific metabolic burden improved models based on whole-body MTV or TLG (p = 0.003 and p = 0.001, respectively), whereas whole-body MTV provided no additional prognostic information once compartment-specific burden was considered (p = 0.90). Bone_TLG, but not binary bone involvement, independently predicted OS, and its prognostic contribution increased over time.

CONCLUSION

In this exploratory analysis, the anatomical distribution of metabolic tumor burden appeared to carry prognostic information beyond conventional whole-body PET metrics. These findings are hypothesis-generating, and prospective multicenter validation is warranted before compartment-specific metabolic phenotyping could inform clinical risk stratification in HER2-positive metastatic breast cancer.