Purpose. Increasing the central dose for large, locally advanced, drug-resistant gastrointestinal stromal tumors (LADR-GISTs) has consistently been a significant challenge. This study explores the feasibility of using multiple shell structures within the tumor to enhance the central ablation dose of large LADR-GIST by increasing the shell doses. Methods and Materials. This study involved five patients with large LADR-GIST who were treated with CyberKnife. The gross tumor volume (GTV) was delineated as a multi-shell structure. Five dose escalation plans (SIB-SBRT) were created for each patient, varying the dose escalation ratios. The radiation doses for the center of the GTV (GTV center) in these plans ranged from 49 Gy to 70 Gy. Parameter evaluations were conducted comparing the SIB-SBRT plans with conventional SBRT plans (Con-SBRT), focusing on equivalent uniform dose (EUD), relative equivalent uniform dose (rEUD), dose volume parameters, conformal index (CI), new conformal index (nCI), gradient index (GI), and monitor unit (MU). The Friedman Test was employed to determine statistical differences (P < 0.05), followed by pairwise comparisons. Results. When the dose escalation ratios reached 25% of the prescribed dose, the average rEUD increased to 6.92, and the proportion of the GTV volume with Biologically Equivalent Dose (BED)> 100 Gy increased to 30.69%. At dose escalation ratios of 30% of the prescribed dose, the rEUD stabilized, but the radiation dose received by the bladder, colon, and duodenum significantly increased. Except for the SIB25-SBRT and SIB30-SBRT groups, no statistically significant differences were observed between the other SIB-SBRT groups and the Con-SBRT group across various evaluation metrics. Conclusions. The method of synchronously increasing the dose using a multi-shell structure is feasible for stereotactic ablation in the treatment of LADR-GISTs using CyberKnife. The results indicate that dose escalation ratios of 25% of the prescribed dose can provide a satisfactory ablation dose (BED > 100 Gy), covering 31% of the large tumor volume.
