Escalation of radiotherapy dose in large locally advanced drug-resistant gastrointestinal stromal tumors by multi-shell simultaneous integrated boost intensity-modulated technique: a feasibility study

BACKGROUND: Resistance to conventional dose schemes and radiotoxicity of healthy tissue is a clinical challenge in the radiation therapy of large locally advanced drug-resistant gastrointestinal stromal tumor (LADR-GIST). This study aimed to assess the feasibility of using multi-shell Simultaneous Integrated Boost Intensity-Modulated modality (SIB-IMRT) strategy to provide a safe and effective escalation dose regimen for LADR-GIST. METHODS: 7 patients with LADR-GIST were selected in this study. The modified SIB-IMRT plans for all patients were generated by delivering different escalation-dose gradients to four ring shaped regions (shells) within the gross tumor volume (GTV). The doses of the central volume of the tumor (GTV(center)) were escalated up to 70–92.5 Gy (25 fractions), while the doses of planning target volume (PTV) and shell-1 were kept at 50.0 Gy. Based on different escalation-dose gradients, the modified SIB-IMRT plans were divided into four groups (SIB-IMRT groups). For comparison purposes, plans obtained by conventional IMRT technique (Con-IMRT) with 50 Gy (25 fractions) were also generated for all patients (Con-IMRT group). All plans were normalized to cover 95% of the PTV with the prescribed dose of 50.0 Gy. The equivalent uniform dose (EUD), relative equivalent uniform dose (rEUD), dose volume histogram (DVH), dose profile, conformity index (CI) and monitor unit (MU) were evaluated in five groups. The Friedman Test was performed to determine whether there were significant differences (P < 0.05). RESULTS: Compared with the Con-IMRT group, the EUD of GTV (EUD(GTV)) and rEUD of SIB-IMRT groups were improved when escalation-dose gradient was increased, and the improvement became significant when the escalation-dose gradient reached 20% of the prescription dose. The rEUD tended to be stable as the escalation-dose gradient went up to 25% of the prescription dose. There were no significant differences in CIs and DVH metrics for OARs between the Con-IMRT group and any SIB-IMRT group, but the significant differences were observed between the SIB(10)-IMRT group and the SIB(25)-IMRT group. For the SIB-IMRT groups, as the dose gradient became steeper in the dose profiles, the higher dose was mainly accumulated in the inner part of GTV accompanied with a higher MU. CONCLUSIONS: The proposed multi-shell SIB-IMRT strategy is feasible in dosimetry for LADR-GIST and can acquire higher therapeutic gain without sacrifice of healthy tissues. It appears that the scheme of delivering 20% of the prescribed escalation-dose gradient to the target volume can provide satisfactory dose irradiation for LADR-GIST, and it should be evaluated in future clinical study.