ESTRO 2024 - Abstract Book

S1804

Clinical - Lung

ESTRO 2024

NK cell functionality changes were also measured via 3 lung cancer cell lines, pokeweed mitogen and tetanus toxoid. Two sample t-test was used to determine the statistical significance.

Results:

Average percentage reductions on integral doses, and V5 (volume receiving a 5Gy dose) of optimized compared to standard plans are: aorta: 26%, 41% heart: 8%, 33%, vena cava: 32%, 52%, T spine: 51%, 81%, lymph nodes: 35%, 57%, total lung- ITV: 1.6%, 1%, body: 10%, 14%. In the standard arm, 20% of patients experienced grade 3 lymphopenia post-SBRT, while none in the optimized arm were lymphopenic. Standard arm had an Absolute Lymphocyte Count (ALC) reduction of 30% at one week post Tx and a nadir at 4 weeks with a 34% reduction. Absolute percentage reductions in ALC from baseline in the optimized arm compared to the standard arm: end of treatment point (15%, p=0.01), 4 weeks (12%, p=0.05), 6 months (15%, p=0.1), and all three time points together 13% (p =0.001). ALC recovery is faster in the optimized arm. When the dataset was divided into central and peripheral tumors, central tumors had the highest improvements in the optimized arm: end of treatment point (31.3%, p=0.004), 4 weeks (11.2%, p=0.03), 6 months (15.5%, p=0.01), and all three time points together 13% (p =0.001). Radiation induced suppression of all blood cell types are also reduced in the optimized arm with respect to standard arm (relative percentages): ALC (38%), WBC (44%), RBC (51%), platelets (44%), monocytes (94%), and neutrophils (50%) at 4-week mark. 32% patients had a net immune increase post SBRT in the optimized arm compared to 6% in the standard arm. Significant functionality changes observed are: Four-week post SBRT ALC increase is positively correlated with response to PWM IgG diff (0.33, p=0.02). Response to H292 and K562 lung cancer cell lines were negatively correlated with Heart +great vessel mean dose (-0.33 p=0.02; -0.31 p=0.03 respectively), and V5 (-0.30 p=0.04 on K562).

Conclusion:

For the first time, we show that it is possible to significantly reduce RIIS compared to standard of care, via optimized RT planning using a predictive model. We have also observed static organ dose volumes that significantly correlate with T cell sub type changes and lymphocyte functionality changes. This has implications in increasing the efficacy of immunotherapy by preserving the existing tumor reactive T cells in the immune system to enhance anti-tumor activity.

Keywords: SBRT, immune suppression, early stage