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preliminary sinonasal sbrt radiobiology

Regional lymph node irradiation altered immune responses after sinonasal stereotactic radiotherapy in dogs

Regional lymph node irradiation was linked to attenuated local cytokine shifts and nodal damage and cell-death signatures after sinonasal stereotactic radiotherapy.

RadOncToday · ·1 min read

KEY POINTS

  • This randomized pilot study included six companion dogs with naturally occurring sinonasal tumors and no identified nodal or distant metastases. Dogs received 30 Gy in 3 daily fractions to the primary tumor alone or to the tumor plus bilateral mandibular and retropharyngeal lymph nodes.
  • Nasal cytokine analysis included two dogs treated to the tumor alone and three dogs receiving additional nodal irradiation. After the second fraction, increases in interleukin-6, interleukin-8, interleukin-10, interferon gamma-induced protein 10, and tumor necrosis factor were observed when nodes were spared but not when they were irradiated; formal between-group statistical testing was not possible.
  • Previously reported flow-cytometry data from the same cohort showed lower local CD4-positive and CD8-positive T-cell populations after the final fraction when regional nodes were irradiated (p=0.038 and p=0.045, respectively).
  • At two weeks, conventional immunohistochemistry found no significant differences in overall nodal immune-cell densities. Multiplex imaging showed higher damage, apoptosis, and dendritic-cell markers in irradiated nodes, with significantly higher HLA-DR expression across nodal regions (p=0.0011).
  • Transcriptomic analysis identified 21 upregulated and 38 downregulated genes in irradiated nodes. Enriched pathways involved regulated cell death, p53 signaling, DNA repair, and antigen cross-presentation, whereas spared nodes retained signatures associated with effector T cells and immune-cell migration and adhesion.

CLINICAL TAKEAWAY

Regional lymph node irradiation may alter both local inflammatory signaling and the immune state of nodal tissue, supporting further investigation of nodal-sparing or treatment-sequencing strategies. However, this was an underpowered canine pilot using a three-fraction regimen, mixed histologies, no immunotherapy, and a single nodal sampling timepoint, so the findings are preliminary and not directly applicable to human treatment planning.

SOURCE

International Journal of Radiation Oncology, Biology, Physics