Regnery Sebastian, Katsigiannopulos Efthimios, Hoegen Philipp, Weykamp Fabian, Sandrini Elisabetta, Held Thomas, Deng Maximilian, Eichkorn Tanja, Buchele Carolin, Rippke Carolin, Renkamp C Katharina, König Laila, Lang Kristin, Thomas Michael, Winter Hauke, Adeberg Sebastian, Klüter Sebastian, Debus Jürgen, Hörner-Rieber Juliane
Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany; National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Im Neuenheimer Feld 400, 69120 Heidelberg, Germany; National Center for Tumor Diseases (NCT), Heidelberg, Germany.
Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
Lung Cancer. 2023 May;179:107175. doi: 10.1016/j.lungcan.2023.03.011. Epub 2023 Mar 21.
Stereotactic radiotherapy of ultracentral lung tumors (ULT) is challenging as it may cause overdoses to sensitive mediastinal organs with severe complications. We aimed to describe long-term outcomes after stereotactic magnetic resonance (MR)-guided online adaptive radiotherapy (SMART) as an innovative treatment of ULT.
PATIENTS & METHODS: We analyzed 36 patients that received SMART to 40 tumors between 02/2020 - 08/2021 inside prospective databases. ULT were defined by planning target volume (PTV) overlap with the proximal bronchial tree or esophagus. We calculated Kaplan Meier estimates for overall survival (OS) and progression-free survival (PFS), and competing risk estimates for the incidence of tumor progression and treatment-related toxicities. ULT patients (N = 16) were compared to non-ULT patients (N = 20).
Baseline characteristics were similar between ULT and non-ULT, but ULT were larger (median PTV: ULT 54.7 cm, non-ULT 19.2 cm). Median follow-up was 23.6 months. ULT and non-ULT showed a similar OS (2-years: ULT 67%, non-ULT 60%, p = 0.7) and PFS (2-years: ULT 37%, non-ULT 34%, p = 0.73). Progressions occurred mainly at distant sites (2-year incidence of distant progression: ULT 63%, non-ULT 61%, p = 0.77), while local tumor control was favorable (2-year incidence of local progression: ULT 7%, non-ULT 0%, p = 0.22). Treatment of ULT led to significantly more toxicities ≥ grade (G) 2 (ULT: 9 (56%), non-ULT: 1 (5%), p = 0.002). Most toxicities were moderate (G2). Two ULT patients developed high-grade toxicities: 1) esophagitis G3 and bronchial bleeding G4 after VEGF treatment, 2) bronchial bleeding G3. Estimated incidence of high-grade toxicities was 19% (3-48%) in ULT, and no treatment-related death occurred.
Our small series supports SMART as potentially effective treatment of ULT. SMART with careful fractionation could reduce severe complications, but treatment of ULT remains a high-risk procedure and needs careful benefit-risk-assessment.
超中央型肺癌肿瘤（ULT）的立体定向放射治疗具有挑战性，因为它可能会对敏感的纵隔器官造成过量照射并引发严重并发症。我们旨在描述立体定向磁共振（MR）引导的在线自适应放射治疗（SMART）作为ULT的一种创新治疗方法的长期疗效。
我们分析了前瞻性数据库中2020年2月至2021年8月期间接受SMART治疗40个肿瘤的36例患者。ULT通过计划靶体积（PTV）与近端支气管树或食管重叠来定义。我们计算了总生存期（OS）和无进展生存期（PFS）的Kaplan-Meier估计值，以及肿瘤进展和治疗相关毒性发生率的竞争风险估计值。将ULT患者（N = 16）与非ULT患者（N = 20）进行比较。
ULT和非ULT患者的基线特征相似，但ULT的肿瘤更大（PTV中位数：ULT为54.7 cm，非ULT为19.2 cm）。中位随访时间为23.6个月。ULT和非ULT患者的OS相似（2年：ULT为67%，非ULT为60%，p = 0.7），PFS也相似（2年：ULT为37%，非ULT为34%，p = 0.73）。进展主要发生在远处部位（2年远处进展发生率：ULT为63%，非ULT为61%，p = 0.77），而局部肿瘤控制良好（2年局部进展发生率：ULT为7%，非ULT为0%，p = 0.22）。ULT治疗导致≥2级（G）毒性的情况明显更多（ULT：9例（56%），非ULT：1例（5%），p = 0.002）。大多数毒性为中度（G2）。2例ULT患者出现了高级别毒性：1例在接受VEGF治疗后发生G3级食管炎和G4级支气管出血；2例发生G3级支气管出血。ULT患者高级别毒性的估计发生率为19%（3%-48%），且未发生与治疗相关的死亡。
我们的小样本研究支持SMART作为ULT的潜在有效治疗方法。谨慎分割剂量的SMART可减少严重并发症，但ULT治疗仍然是一项高风险程序，需要仔细进行获益风险评估。
