Abstract：
OBJECTIVE: To assess the robustness and to define the dosimetric and NTCP advantages of pencil-beam-scanning proton therapy (PBSPT) compared with VMAT for unresectable Stage III non-small lung cancer (NSCLC) in the immunotherapy era.
METHODS: 10 patients were re-planned with VMAT and PBSPT using: 1) ITV-based robust optimization with 0.5 cm setup uncertainties and (for PBSPT) 3.5 % range uncertainties on free-breathing CT 2) CTV-based RO including all 4DCTs anatomies. Target coverage (TC), organs at risk dose and TC robustness (TCR), set at V95%, were compared. The NTCP risk for radiation pneumonitis (RP), 24-month mortality (24MM), G2 + acute esophageal toxicity (ET), the dose to the immune system (EDIC) and the left anterior descending (LAD) coronary artery V15 < 10 % were registered. Wilcoxon test was used.
RESULTS: Both PBSPT methods improved TC and TCR (p < 0.01). The mean lung dose and lung V20 were lower with PBSPT (p < 0.01). Median mean heart dose reduction with PBSPT was 8 Gy (p < 0.001). PT lowered median LAD V15 (p = 0.004). ΔNTCP > 5 % with PBSPT was observed for two patients for RP and for five patients for 24 MM. ΔNTCP for ≥ G2 ET was not in favor of PBSPT for all patients. PBSPT halved median EDIC (4.9/5.1 Gy for ITV/CTV-based VMAT vs 2.3 Gy for both ITV/CTV-based PBSPT, p < 0.01).
CONCLUSIONS: PBSPT is a robust approach with significant dosimetric and NTCP advantages over VMAT; the EDIC reduction could allow for a better integration with immunotherapy. A clinical benefit for a subset of NSCLC patients is expected.
METHODS: 10 patients were re-planned with VMAT and PBSPT using: 1) ITV-based robust optimization with 0.5 cm setup uncertainties and (for PBSPT) 3.5 % range uncertainties on free-breathing CT 2) CTV-based RO including all 4DCTs anatomies. Target coverage (TC), organs at risk dose and TC robustness (TCR), set at V95%, were compared. The NTCP risk for radiation pneumonitis (RP), 24-month mortality (24MM), G2 + acute esophageal toxicity (ET), the dose to the immune system (EDIC) and the left anterior descending (LAD) coronary artery V15 < 10 % were registered. Wilcoxon test was used.
RESULTS: Both PBSPT methods improved TC and TCR (p < 0.01). The mean lung dose and lung V20 were lower with PBSPT (p < 0.01). Median mean heart dose reduction with PBSPT was 8 Gy (p < 0.001). PT lowered median LAD V15 (p = 0.004). ΔNTCP > 5 % with PBSPT was observed for two patients for RP and for five patients for 24 MM. ΔNTCP for ≥ G2 ET was not in favor of PBSPT for all patients. PBSPT halved median EDIC (4.9/5.1 Gy for ITV/CTV-based VMAT vs 2.3 Gy for both ITV/CTV-based PBSPT, p < 0.01).
CONCLUSIONS: PBSPT is a robust approach with significant dosimetric and NTCP advantages over VMAT; the EDIC reduction could allow for a better integration with immunotherapy. A clinical benefit for a subset of NSCLC patients is expected.
摘要：
目的：评估笔形束扫描质子治疗（PBSPT）与VMAT相比在免疫治疗时代不可切除的III期非小细胞肺癌（NSCLC）的稳健性，并确定其剂量学和NTCP优势。
方法：使用VMAT和PBSPT对10例患者进行了重新计划，使用：1）基于ITV的稳健优化，具有0.5cm的设置不确定性和（对于PBSPT）在自由呼吸CT上的3.5％范围不确定性2）基于CTV的RO包括所有4DCT解剖结构。目标覆盖率（TC），风险器官剂量和TC稳健性(TCR)，设置在V95%，进行了比较。放射性肺炎（RP）的NTCP风险，24个月死亡率（24MM），G2+急性食管毒性（ET），记录免疫系统(EDIC)和左前降支(LAD)冠状动脉V15<10%的剂量。使用Wilcoxon检验。
结果：两种PBSPT方法均可改善TC和TCR（p<0.01）。PBSPT的平均肺剂量和肺V20较低(p<0.01)。PBSPT的平均心脏剂量减少中位数为8Gy(p<0.001)。PT降低了中位数LADV15（p=0.004）。对于2例RP患者和5例24MM患者，观察到PBSPT的ΔNTCP>5％。≥G2ET的ΔNTCP对所有患者均不赞成PBSPT。PBSPT将EDIC中位数减半（基于ITV/CTV的VMAT为4.9/5.1Gy，基于ITV/CTV的PBSPT为2.3Gy，p<0.01)。
结论：PBSPT是一种稳健的方法，与VMAT相比具有显著的剂量学和NTCP优势；降低EDIC可以更好地与免疫治疗结合。预期NSCLC患者的子集的临床益处。
方法：使用VMAT和PBSPT对10例患者进行了重新计划，使用：1）基于ITV的稳健优化，具有0.5cm的设置不确定性和（对于PBSPT）在自由呼吸CT上的3.5％范围不确定性2）基于CTV的RO包括所有4DCT解剖结构。目标覆盖率（TC），风险器官剂量和TC稳健性(TCR)，设置在V95%，进行了比较。放射性肺炎（RP）的NTCP风险，24个月死亡率（24MM），G2+急性食管毒性（ET），记录免疫系统(EDIC)和左前降支(LAD)冠状动脉V15<10%的剂量。使用Wilcoxon检验。
结果：两种PBSPT方法均可改善TC和TCR（p<0.01）。PBSPT的平均肺剂量和肺V20较低(p<0.01)。PBSPT的平均心脏剂量减少中位数为8Gy(p<0.001)。PT降低了中位数LADV15（p=0.004）。对于2例RP患者和5例24MM患者，观察到PBSPT的ΔNTCP>5％。≥G2ET的ΔNTCP对所有患者均不赞成PBSPT。PBSPT将EDIC中位数减半（基于ITV/CTV的VMAT为4.9/5.1Gy，基于ITV/CTV的PBSPT为2.3Gy，p<0.01)。
结论：PBSPT是一种稳健的方法，与VMAT相比具有显著的剂量学和NTCP优势；降低EDIC可以更好地与免疫治疗结合。预期NSCLC患者的子集的临床益处。
