Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado; Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania.
Department of Radiation Oncology, Emory University, Atlanta, Georgia.
Int J Radiat Oncol Biol Phys. 2022 Mar 15;112(4):986-995. doi: 10.1016/j.ijrobp.2021.10.147. Epub 2021 Nov 9.
Radiation pneumonitis remains a major limitation in the radiation therapy treatment of patients with lung cancer. Functional avoidance radiation therapy uses functional imaging to reduce pulmonary toxic effects by designing radiation therapy plans that reduce doses to functional regions of the lung. Lung functional imaging has been developed that uses 4-dimensional computed tomography (4DCT) imaging to calculate 4DCT-based lung ventilation (4DCT-ventilation). A phase 2 multicenter study was initiated to evaluate 4DCT-ventilation functional avoidance radiation therapy. The study hypothesis was that functional avoidance radiation therapy could reduce the rate of grade ≥2 radiation pneumonitis to 12% compared with a 25% historical rate, with the trial being positive if ≤16.4% of patients experienced grade ≥2 pneumonitis.
Lung cancer patients receiving curative-intent radiation therapy (prescription doses of 45-75 Gy) and chemotherapy were accrued. Patient 4DCT scans were used to generate 4DCT-ventilation images. The 4DCT-ventilation images were used to generate functional avoidance plans that reduced doses to functional portions of the lung while delivering the prescribed tumor dose. Pneumonitis was evaluated by a clinician at 3, 6, and 12 months after radiation therapy.
Sixty-seven evaluable patients were accrued between April 2015 and December 2019. The median prescription dose was 60 Gy (range, 45-66 Gy) delivered in 30 fractions (range, 15-33 fractions). The average reduction in the functional volume of lung receiving ≥20 Gy with functional avoidance was 3.5% (range, 0%-12.8%). The median follow-up was 312 days. The rate of grade ≥2 radiation pneumonitis was 10 of 67 patients (14.9%; 95% upper CI, 24.0%), meeting the phase 2 criteria.
4DCT-ventilation offers an imaging modality that is convenient and provides functional imaging without an extra procedure necessary. This first report of a multicenter study of 4DCT-ventilation functional avoidance radiation therapy provided data showing that the trial met phase 2 criteria and that evaluation in a phase 3 study is warranted.
放射性肺炎仍然是肺癌患者放射治疗的主要限制因素。功能性回避放射治疗使用功能成像来降低肺毒性效应，通过设计减少肺功能区域剂量的放射治疗计划。已经开发出肺功能成像，使用 4 维 CT（4DCT）成像来计算基于 4DCT 的肺通气（4DCT-ventilation）。启动了一项多中心 2 期研究来评估 4DCT-ventilation 功能性回避放射治疗。该研究的假设是，与 25%的历史发生率相比，功能性回避放射治疗可以将≥2 级放射性肺炎的发生率降低至 12%，如果≤16.4%的患者出现≥2 级肺炎，则试验为阳性。
入组接受根治性放射治疗（处方剂量 45-75 Gy）和化疗的肺癌患者。患者的 4DCT 扫描用于生成 4DCT-ventilation 图像。使用 4DCT-ventilation 图像生成功能性回避计划，在给予规定肿瘤剂量的同时减少肺功能部分的剂量。通过临床医生在放射治疗后 3、6 和 12 个月评估肺炎。
2015 年 4 月至 2019 年 12 月共入组 67 例可评估患者。中位处方剂量为 60 Gy（范围，45-66 Gy），分 30 次（范围，15-33 次）。功能性回避时接受≥20 Gy 的功能性肺体积的平均减少量为 3.5%（范围，0%-12.8%）。中位随访时间为 312 天。≥2 级放射性肺炎的发生率为 67 例患者中有 10 例（14.9%；95%上限 CI，24.0%），符合 2 期标准。
4DCT-ventilation 提供了一种方便的成像方式，无需额外的程序即可提供功能成像。这是多中心 4DCT-ventilation 功能性回避放射治疗研究的首次报告，提供的数据表明该试验符合 2 期标准，值得进行 3 期研究。
