局部晚期非小细胞肺癌（NSCLC）治疗后的局部失败率仍然很高。通过统一剂量递增或剂量递增至治疗中期 PET 亲和残留病灶来改善局部控制的努力因毒性增加而受到限制。该试验旨在通过在治疗中期结合 FDG-PET 和 V/Q SPECT 成像来完善基于反应的适应性放疗 (RT) 并最大程度地降低毒性。47 名 IIA-III 期不可切除 NSCLC 患者前瞻性地参加了这项单机构试验（ NCT02492867）。患者接受同步放化疗，并结合基于 V/Q SPECT 和 FDG-PET 的 30 多个分次的基于个性化反应的适应性放疗。前 21 次分次（46.2Gy，2.2 Gy/分次）被递送至肿瘤，同时最大限度地减少 SPECT 定义的功能性肺的剂量。然后，根据治疗中期 FDG-PET 肿瘤反应，对最后 9 个分次（2.2-3.8Gy/分次）进行调整，直至总共 80.4Gy，以逐步增加残余肿瘤的剂量，同时最大限度地减少 SPECT 定义的功能剂量。肺。非进展患者接受巩固卡铂/紫杉醇或度瓦鲁单抗治疗。该研究的主要终点是≥2级肺和食道毒性。次要终点包括局部进展时间、肿瘤反应和总生存率。治疗一年后，2 级和 3 级肺炎发生率分别为 21.3% 和 2.1%，接受治疗的患者的肺炎发生率没有差异且未接受 durvalumab 辅助治疗 (p=0.74)。虽然没有出现 3 级食管相关毒性，但 66.0% 的患者出现了 2 级食管炎。 1 年和 2 年局部控制率分别为 94.5%（95% CI，87.4% - 100%）和 87.5%（95% CI，76.7% - 100%）。 1 年总生存率为 82.8%（95% CI，72.6% -94.4%），2 年总生存率为 62.3%（95% CI，49.6%-78.3%）。基于反应的自适应剂量递增考虑了肿瘤变化和正常情况治疗期间的组织功能提供了出色的局部控制，毒性与标准放化疗相当，并且不会增加辅助免疫治疗的毒性。版权所有 © 2024。由 Elsevier Inc. 出版。

Local failure rates after treatment for locally advanced non-small-cell lung cancer (NSCLC) remain high. Efforts to improve local control with uniform dose-escalation or dose-escalation to mid-treatment PET-avid residual disease have been limited by heightened toxicity. This trial aimed to refine response-based adaptive radiation (RT) and minimize toxicity by incorporating FDG-PET and V/Q SPECT imaging mid-treatment.47 patients with Stage IIA-III unresectable NSCLC were prospectively enrolled in this single-institution trial (NCT02492867). Patients received concurrent chemoradiation with personalized response-based adaptive RT over 30 fractions incorporating V/Q SPECT and FDG-PET. The first 21 fractions (46.2Gy at 2.2 Gy/fraction) were delivered to the tumor while minimizing dose to SPECT-defined functional lung. The plan was then adapted for the final 9 fractions (2.2-3.8Gy/fraction) up to a total of 80.4Gy, based on mid-treatment FDG-PET tumor response to escalate dose to residual tumor while minimizing dose to SPECT-defined functional lung. Non-progressing patients received consolidative carboplatin/paclitaxel or durvalumab. The primary endpoint of the study was ≥ grade 2 lung and esophageal toxicities. Secondary endpoints included time to local progression, tumor response, and overall survival.At one year post-treatment, the rates of grade 2 and grade 3 pneumonitis were 21.3% and 2.1%, respectively, with no difference in pneumonitis rates among patients who received and did not receive adjuvant durvalumab (p=0.74). While there were no grade 3 esophageal-related toxicities, 66.0% of patients experienced grade 2 esophagitis. 1- and 2-year local control rates were 94.5% (95% CI, 87.4% - 100%) and 87.5% (95% CI, 76.7% - 100%), respectively. Overall survival was 82.8% (95% CI, 72.6% -94.4%) at 1 year and 62.3% (95% CI, 49.6%-78.3%) at 2 years.Response-based adaptive dose-escalation accounting for tumor change and normal tissue function during treatment provided excellent local control, comparable toxicity to standard chemoradiation, and did not increase toxicity with adjuvant immunotherapy.Copyright © 2024. Published by Elsevier Inc.