Low Radiation Doses to Gross Tumor Volume in Metabolism Guided Lattice Irradiation Based on Lattice-01 Study: Dosimetric Evaluation and Potential Clinical Research Implication

<b>Purpose</b>: This paper aims to calculate the gross tumor volume (GTV) receiving low radiation doses in patients submitted to "metabolism-guided" lattice radiation therapy and relative possible implications with clinical outcomes. <b>Material and Methods</b>: We reviewed plans for treating voluminous masses via "metabolism-guided" LATTICE-01 irradiation. The aim was to deliver high-dose radiation to spherical deposits (vertices) within a bulky tumor mass. These were placed at tumor areas with differing PET metabolism. We evaluated the relationships between GTV volumes and dose-volumetric histograms (mean, maximum, minimum, and % GTV received 0.5, 1, 2, 3 Gy). <b>Results</b>: Sixty-two plans of treatment met the inclusion criteria as established. The median GTV volume was 315.9 cc (range = 10.54-2605.9 cc). A median of two Vertices was allocated within the GTVs (range 1-9) and were planned to receive a dose of ≥10 Gy/1 fraction (median 12 Gy, range 10-15 Gy). Median V3Gy percentage was 51.58% (range 2-100%), median V2Gy percentage was 67.80% (range 1.60-100%), median V1Gy percentage was 83.70% (range 0.80-100%), and median V0.5Gy percentage was 88.49% (range 17.60-100%). <b>Conclusions</b>: In the present series, we performed a dosimetric evaluation of the GTV's volume exposed to low doses during the metabolic guided lattice irradiation process. Combining high- and low-dose radiotherapy based on a spatially fractionated (LATTICE) approach could reactivate the immune system against cancer cells. These observations could be useful for planning prospective studies on immunotherapy combined with the lattice technique.