Eichkorn Tanja, Lischalk Jonathan W, Stüwe Cedric, Tonndorf-Martini Eric, Schubert Kai, Dinges Lisa-Antonia, Regnery Sebastian, Bozorgmehr Farastuk, König Laila, Christopoulos Petros, Hörner-Rieber Juliane, Adeberg Sebastian, Herfarth Klaus, Winter Hauke, Thomas Michael, Rieken Stefan, Debus Jürgen, El Shafie Rami A
Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany.
National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg, Germany.
Front Oncol. 2023 Jan 13;12:1035370. doi: 10.3389/fonc.2022.1035370. eCollection 2022.
A very narrow therapeutic window exists when delivering curative chemoradiotherapy for inoperable locally advanced non-small cell lung cancer (NSCLC), particularly when large distances exist between areas of gross disease in the thorax. In the present study, we hypothesize that a novel technique of stereotactic body radiation therapy (SBRT) to the primary tumor in combination with volumetric arc therapy (VMAT) to the mediastinal lymph nodes (MLN) is a suitable approach for high-risk patients with large volume geographically distant locally advanced NSCLC.
In this single institutional review, we identified high-risk patients treated between 2014 and 2017 with SBRT to the parenchymal lung primary as well as VMAT to the involved MLN using conventional fractionation. Dosimetrically, comparative plans utilizing VMAT conventionally fractionated delivered to both the primary and MLN were analyzed. Clinically, toxicity (CTCAE version 5.0) and oncologic outcomes were analyzed in detail.
A total of 21 patients were identified, 86% (n=18) of which received chemotherapy as a portion of their treatment. As treatment phase was between 2014 and 2017, none of the patients received consolidation immunotherapy. Target volume (PTV) dose coverage (99 vs. 87%) and CTV volume (307 vs. 441 ml) were significantly improved with SBRT+MLN vs. for VMAT alone (p<0.0001). Moreover, low-dose lung (median V5Gy [%]: 71 vs. 77, p<0.0001), heart (median V5Gy [%]: 41 vs. 49, p<0.0001) and esophagus (median V30Gy [%]: 54 vs. 55, p=0.03) dose exposure were all significantly reduced with SBRT+MLN. In contrast, there was no difference observed in high-dose exposure of lungs, heart, and spinal cord. Following SBRT+MLN treatment, we identified only one case of high-grade pneumonitis. As expected, we observed a higher rate of esophagitis with a total of seven patients experience grade 2+ toxicity. Overall, there were no grade 4+ toxicities identified. After a median 3 years follow up, disease progression was observed in 70% of patients irradiated using SBRT+MLN, but never in the spared 'bridging' tissue between pulmonary SBRT and mediastinal VMAT.
For high risk patients, SBRT+MLN is dosimetrically feasible and can provide an alternative to dose reductions necessitated by otherwise very large target volumes.
对于无法手术的局部晚期非小细胞肺癌（NSCLC）进行根治性放化疗时，治疗窗口非常狭窄，尤其是当胸部大体病变区域之间距离较大时。在本研究中，我们假设一种针对原发性肿瘤的立体定向体部放射治疗（SBRT）新技术与针对纵隔淋巴结（MLN）的容积弧形调强放疗（VMAT）相结合，对于具有大体积、地理上远距离的局部晚期NSCLC的高危患者是一种合适的方法。
在这项单机构回顾研究中，我们确定了2014年至2017年间接受SBRT治疗肺部实质原发性肿瘤以及VMAT治疗受累MLN的高危患者，采用传统分割方式。在剂量学方面，分析了使用传统分割的VMAT对原发性肿瘤和MLN进行照射的对比计划。在临床方面，详细分析了毒性（CTCAE 5.0版）和肿瘤学结果。
共确定了21例患者，其中86%（n = 18）接受了化疗作为其治疗的一部分。由于治疗阶段在2014年至2017年之间，没有患者接受巩固性免疫治疗。与单纯VMAT相比，SBRT + MLN显著提高了靶区体积（PTV）剂量覆盖（99%对87%）和临床靶区体积（307 ml对441 ml）（p < 0.0001）。此外，SBRT + MLN显著降低了低剂量肺（V5Gy中位数[％]：71%对77%，p < 0.0001）、心脏（V5Gy中位数[％]：41%对49%，p < 0.0001）和食管（V30Gy中位数[％]：54%对55%，p = 0.03）的剂量暴露。相比之下，在肺、心脏和脊髓的高剂量暴露方面未观察到差异。在SBRT + MLN治疗后，我们仅发现1例重度肺炎病例。正如预期的那样，我们观察到食管炎发生率较高，共有7例患者出现2级及以上毒性。总体而言，未发现4级及以上毒性。经过中位3年的随访，使用SBRT + MLN照射的患者中有70%出现疾病进展，但在肺部SBRT和纵隔VMAT之间的未照射“桥接”组织中从未出现。
对于高危患者，SBRT + MLN在剂量学上是可行的，并且可以为因靶区体积过大而需要降低剂量的情况提供一种替代方案。
