Weisman Michael, Durm Greg, Shields Misty Dawn, Hanna Nasser H, Althouse Sandra, Lautenschlaeger Tim
Department of Radiation Oncology, Indiana University School of Medicine.
Department of Medicine, Division of Hematology/Oncology, Indiana University School of Medicine.
Int J Radiat Oncol Biol Phys. 2025 Mar 1;121(3):720-727. doi: 10.1016/j.ijrobp.2024.09.050. Epub 2024 Oct 26.
The addition of immunotherapy (IO) after concurrent chemoradiation therapy (CCRT) for unresectable non-small cell lung cancer (NSCLC) has become common practice in eligible patients. Approaches to further improve outcomes and reduce treatment-related toxicity for these patients are needed. This study evaluates the risk of radiation pneumonitis after CCRT and its correlation with the radiation dose distribution, IO regimen (nivolumab vs nivolumab plus ipilimumab), and patient demographics across BTCRC-LUN16-081.
Patients with unresectable stage III NSCLC after completion of CCRT were enrolled in BTCRC-LUN16-081, a randomized phase 2 trial to assess the efficacy and tolerability of consolidative nivolumab versus nivolumab plus ipilimumab for 6 months. Radiation dose parameters, patient demographics, and toxicity events were evaluated among treatment arms for risk and severity of pneumonitis.
One hundred-five patients were enrolled into 2 treatment arms; 54 patients received nivolumab alone, and 51 patients received nivolumab plus ipilimumab. Of these, 104 patients had dose-volume histogram information available. Within this cohort, 65 patients (62.5%) had stage IIIA, and 39 patients (37.5%) had stage IIIB NSCLC disease, per the American Journal Committee on Cancer, seventh edition. During the study, 29 patients (27.9%) were diagnosed with grade 2 or greater pneumonitis. Using logistic regression and evaluating different cutoffs for percentage of normal lung volume receiving at least 20 gy (V20), patients with V20 > 23% demonstrated significantly higher grade 2 or greater pneumonitis rates (37.1% vs 16.2%, P = .031). No significant difference in rates of pneumonitis between arms was identified. Traditional lung dose-volume histogram cutoffs (percentage of normal lung volume receiving at least 5 gy (V5) > 65%, V20 > 35%, and mean > 20 Gy) were not associated with pneumonitis.
In patients receiving nivolumab or nivolumab plus ipilimumab after definitive CCRT, lung V20 > 23% was associated with an increased risk of grade 2 or greater pneumonitis. Radiation dose constraints for lungs in patients receiving consolidative IO after CCRT should continue to be evaluated and optimized when feasible.
对于不可切除的非小细胞肺癌（NSCLC）患者，同步放化疗（CCRT）后加用免疫治疗（IO）已成为符合条件患者的常用治疗方法。需要进一步改善这些患者的治疗效果并降低治疗相关毒性的方法。本研究评估了CCRT后放射性肺炎的风险及其与放射剂量分布、IO方案（纳武单抗对比纳武单抗联合伊匹木单抗）以及BTCRC-LUN16-081研究中患者人口统计学特征的相关性。
完成CCRT后的不可切除III期NSCLC患者入组BTCRC-LUN16-081研究，这是一项随机2期试验，旨在评估巩固性使用纳武单抗对比纳武单抗联合伊匹木单抗6个月的疗效和耐受性。在各治疗组中评估放射剂量参数、患者人口统计学特征以及肺炎的风险和严重程度等毒性事件。
105例患者被纳入2个治疗组；54例患者仅接受纳武单抗治疗，51例患者接受纳武单抗联合伊匹木单抗治疗。其中，104例患者有剂量体积直方图信息。在该队列中，根据美国癌症联合委员会第七版标准，65例患者（62.5%）为IIIA期，39例患者（37.5%）为IIIB期NSCLC疾病。在研究期间，29例患者（27.9%）被诊断为2级或更高级别的肺炎。使用逻辑回归并评估接受至少20 Gy（V20）的正常肺体积百分比的不同截断值，V20>23%的患者2级或更高级别肺炎发生率显著更高（37.1%对16.2%，P = 0.031）。未发现各治疗组之间肺炎发生率的显著差异。传统的肺剂量体积直方图截断值（接受至少5 Gy（V5）的正常肺体积百分比>65%、V20>35%以及平均剂量>20 Gy）与肺炎无关。
在接受确定性CCRT后使用纳武单抗或纳武单抗联合伊匹木单抗的患者中，肺V20>23%与2级或更高级别肺炎风险增加相关。对于CCRT后接受巩固性IO治疗的患者，肺部的放射剂量限制在可行时应继续进行评估和优化。
