Amygdala metabolic activity on FDG PET is associated with survival, response to immune checkpoint inhibition, and tumor immune signaling in non-small cell lung cancer

Geist, B. K.; Vraka, C.; Mertel, C. T. S.; Beer, L.; Frille, A.; Herbsthofer, L.; Hermann, N.; Hesse, S.; Kenner, L.; Kifjak, D.; Kluge, K.; Kulterer, O. C.; Lapa, C.; Lieblich, A.; Nakuz, T. S.; Oberndorfer, F.; Kain, R.; Prosch, H.; Sabri, O.; Sattler, B.; Schweiger, T.; Aigner, C.; Spielvogel, C.; Tsomaia, D.; Trachtova, K.; Tomberger, M.; Wirtz, H.; Yu, J.; Grünert, S.; Hacker, M.

doi:10.64898/2026.09.10.750685

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bioRxiv · 10.64898/2026.09.10.750685

Amygdala metabolic activity on FDG PET is associated with survival, response to immune checkpoint inhibition, and tumor immune signaling in non-small cell lung cancer

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Abstract

Amygdala metabolic activity (AmygAc) measured by [18F]FDG PET has been associated with chronic psychological stress and adverse clinical outcomes, but its relationship with antitumor immunity and treatment response remains incompletely understood. We investigated AmygAc as a host-derived imaging biomarker in non-small cell lung cancer (NSCLC) and examined its association with survival, response to immune checkpoint inhibition (ICI), and the tumor immune microenvironment. Methods: In this multicenter retrospective study, baseline [18F]FDG PET scans from 256 treatment-naive patients with NSCLC were analyzed to quantify AmygAc. Overall survival was assessed in the full cohort, and treatment response was evaluated in 79 patients who subsequently received neoadjuvant ICI therapy. AmygAc was integrated with clinical and tumor-derived imaging parameters. To investigate its biological correlates, tumor tissue from a selected subcohort was analyzed using multiplex immunofluorescence and spatial transcriptomics.

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Geist, B. K., Vraka, C., Mertel, C. T. S., Beer, L., Frille, A., Herbsthofer, L., Hermann, N., Hesse, S., Kenner, L., Kifjak, D., Kluge, K., Kulterer, O. C., Lapa, C., Lieblich, A., Nakuz, T. S., Oberndorfer, F., Kain, R., Prosch, H., Sabri, O., Sattler, B., Schweiger, T., Aigner, C., Spielvogel, C., Tsomaia, D., Trachtova, K., Tomberger, M., Wirtz, H., Yu, J., Grünert, S., Hacker, M.. 2026-09-13. Amygdala metabolic activity on FDG PET is associated with survival, response to immune checkpoint inhibition, and tumor immune signaling in non-small cell lung cancer. https://doi.org/10.64898/2026.09.10.750685

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