The aim of this study was to clarify the dosimetric advantage of reducing CTV dose with SIB-VMAT for the LA-NSCLC VMAT radiotherapy. The automated planning method was applied to exclude the influence caused by subjective factors. And this approach could implemented straightforward in future clinical practice as saving human labor and guarantee the consistency and quality of VMAT plans. The results showed that SIB-VMAT plans yielded full protection for normal tissues compared to C-VMAT plans, with significant reductions in the doses to lung, heart, esophagus and spinal cord. SIB-VMAT plans got lower SD values than C-VMAT plans, indicating a superior normal-tissue sparing for SIB-VMAT approach.
Radiation-induced pneumonitis (RP) is the most common dose-limiting complication of LA-NSCLC treated by thoracic radiotherapy. Numerous studies indicated that dosimetric parameters, such as mean lung dose (MLD), V5, V10, V20, V30, V40, V50, were associated with the occurrence of RP[17–20]. All metrics above were evaluated in our study. According to the study conducted by sheng et al., total lung V5, V20, V30 and mean dose were all correlated with grade ≥ 2 RP, furthermore, lung V30 was the independent risk factor. Patients with high lung V30 (exceed 14.2%) suffered 2.92-fold increased risk of RP compared to those with low V30 (no more than 14.2%). Other two studies also considered lung V30 as an independent predictor for the occurrence of symptomatic RP[19, 21]. In our study, the SIB-VMAT plans achieved a sharp reduction in lung V30, with median decreased proportion of 8.7%, which would benefit a lot in the reduction of lung toxicities. Xia et al. compared the SIB-IMRT and conventional IMRT plans, and found that the SIB-IMRT plans got lower mean dose, V5 and V20 of total lung. According to the study conducted by Xhaferllari et. al, VMAT is dosimetrically advantageous in treating early-stage NSCLC with SABR compared to fixed-beam IMRT, while providing significantly shorter treatment times. Moreover, they pointed out that no significant difference was observed in the two VMAT techniques (SmartArc (SA) and RapidArc (RA)). No studies dig into the SIB and conventional prescription VMAT plans. As it is widely known that VMAT is superior to IMRT in dosimetric aspect, our study focus on this two type prescription in VMAT plans. SIB-VMAT plans achieved significant reductions in mean dose, V30, V40 and V50 of total lung compared to C-VMAT plans, while lung V5 (P = 0.366), V10 (P = 0.965) and V20 (P = 0.95) were comparable between the two groups. The advantages of SIB-VMAT mainly rest on the reduction of high and inter-median dose exposure in the pulmonary, not significant in low dose exposure.
The cardiac doses have been proved correlated with the outcomes of LA-NSCLC, including both radiation-induced toxicities and overall survival. According to the systematic review conducted by Zhang et al , the heart dose-volume parameters of V5 and V30 were independent predictors for both cardiac events and overall survival among patients with NSCLC. Similarly, Wang et al. found that heart V30 were significantly correlated with cardiac toxicity, including pericardial, ischemic and arrhythmic events. The secondary analysis of RTOG 0617 also indicated that heart V40 was significantly associated with OS for LA-NSCLC (HR 1.012, P＜0.001) . Our study observed obvious dosimetric advantages in heart V30 and V40 in SIB-VMAT plans compared with C-VMAT plans, with decreased proportions of 26.1% and 38.8%. It suggested that SIB-VMAT plan had better performances in heart protection, especially the volume reduction of high and inter-median dose irradiation.
Esophagus toxicity is also a common complication when radiotherapy is delivered to the thorax. Numerous studies has correlated esophagus toxicity with dose-volumetric data for lung cancer patients treated with radiotherapy, including the maximum dose, mean dose and the volume of esophagus receiving 20-70Gy. But the best predictors remained unclear. According to the model made by the Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) group, the rate of acute esophagitis was supposed to surpass 30% as V50 exceed 40%. Other studies also reported that the maximum dose ≥ 58 or 60 Gy was significantly associated with the risk of grade 3–5 esophagus injury[29, 30]. The SIB-VMAT plans achieved significant reductions in maximum dose of esophagus, which will benefit a lot in the prevention of severe esophagitis.
The technique of automated planning was used in VMAT plan design in the present study, and conformal coverage of the PGTV/PTV by the 95% of the prescription dose was well achieved. All plans obtained low values for SD (less than 1), and most ranged from 0 to 0.1. It represented that the plan quality by automated planning technique is promising. Several plans with large volume of PTV (༞600 cc) exceed the OARs constraints, therefore manual intervention in plan design should provide for particular patients with large target volume. At this point, automated plan served as a benchmark for planner (dosimetrists or medical physicists) and radiation oncologists making clinical decision, for example, by sacrificing the conformity or homogeneity of targets, the dose OARs could protect better.
There are several limitations in the present study. Firstly, as a single center and small example size study, the results may be affected by potential confounding factors. Secondly, the plans were generated retrospectively, which were not used in clinical practice. The comparison of the toxicity based on these two prescription type plans is not provided currently. Therefore, further studies are still needed to present the reduced toxicity of SIB-VMAT technique in clinic practice.