{Reference Type}: Journal Article
{Title}: The effective radiation dose to immune cells predicts lymphopenia and inferior cancer control in locally advanced NSCLC.
{Author}: Friedes C;Iocolano M;Lee SH;Duan L;Li B;Doucette A;Cohen RB;Aggarwal C;Sun LL;Levin WP;Cengel KA;Kao G;Teo BK;Langer CJ;Xiao Y;Bradley J;Feigenberg SJ;Yegya-Raman N;
{Journal}: Radiother Oncol
{Volume}: 190
{Issue}: 0
{Year}: 2024 01 24
{Factor}: 6.901
{DOI}: 10.1016/j.radonc.2023.110030
{Abstract}: To explore the association of the effective dose to immune cells (EDIC) with disease control, lymphopenia, and toxicity in patients with non-small cell lung cancer (NSCLC) and identify methods to reduce EDIC.<BR>We abstracted data from all patients with locally advanced NSCLC treated with chemoradiation with or without consolidative immunotherapy over a ten-year period. Associations between EDIC and progression-free survival (PFS) and overall survival (OS) were modeled with Cox proportional hazards and Kaplan-Meier method. Logistic regression was used to model predictors of lymphopenia and higher EDIC. Analyses were performed with EDIC as a continuous and categorical variable. Lymphopenia was graded per CTCAE v5.0.<BR>Overall, 786 patients were included (228 of which received consolidative immunotherapy); median EDIC was 4.7 Gy. Patients with EDIC < 4.7 Gy had a longer median PFS (15.3 vs. 9.0 months; p < 0.001) and OS (34.2 vs. 22.4 months; p < 0.001). On multivariable modeling, EDIC correlated with inferior PFS (HR 1.08, 95 % CI 1.01-1.14, p = 0.014) and OS (HR 1.10, 95 % CI 1.04-1.18, p = 0.002). EDIC was predictive of grade 4 lymphopenia (OR 1.16, 95 % CI 1.02-1.33, p = 0.026). EDIC ≥ 4.7 Gy was associated with increased grade 2 + pneumonitis (6-month incidence: 26 % vs 20 %, p = 0.04) and unplanned hospitalizations (90-day incidence: 40 % vs 30 %, p = 0.002). Compared to protons, photon therapy was associated with EDIC ≥ 4.7 Gy (OR 5.26, 95 % CI 3.71-7.69, p < 0.001) in multivariable modeling.<BR>EDIC is associated with inferior disease outcomes, treatment-related toxicity, and the development of severe lymphopenia. Proton therapy is associated with lower EDIC. Further investigations to limit radiation dose to the immune system appear warranted.