Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway.
Department of Pathology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway.
Acta Oncol. 2021 Feb;60(2):149-156. doi: 10.1080/0284186X.2020.1854851. Epub 2020 Dec 24.
The implementation of immune checkpoint inhibitors (ICI) into the standard care of advanced non-small cell lung cancer (NSCLC) has improved prognosis for this group of patients. However, long-term survival is rare. The aim of the study was to identify predictors of response and, especially, to investigate the impact radiotherapy might have on duration of response.
The association between pretreatment patient/tumor characteristics and progression-free survival (PFS), overall survival (OS), and lung cancer-specific survival was investigated in 78 patients receiving an ICI as ≥2nd line treatment for advanced NSCLC, using Cox regression analysis. Due to competing risk, cause-specific deaths were also examined with cumulative incidence plots.
Median OS was 12.6 months (95% CI 7.8-18.2) and median PFS 4.1 months (95% CI 3.0-6.2), after median follow-up time of 49.7 months (range 20.9-51.5). Increasing CRP and neutrophil/lymphocyte ratio (NLR), were associated with poor PFS (CRP: HR 1.49, 95% CI 1.12-1.98; NLR: HR 1.59, 95% CI 1.22-1.85) and OS (CRP: HR 1.94, 95% CI 1.47-2.56; NLR: HR 1.54, 95% CI 1.27-1.87). Radiotherapy prior to immunotherapy was not significantly associated with patient outcome. However, when the dataset was split at 6 months of follow-up, to be able to identify early and late predictors of prognosis, we found that patients receiving radiotherapy <6 months prior to immunotherapy had better PFS (HR: 0.27, 95% CI 0.09-0.84) and lung cancer-specific survival (HR: 0.41, 95% CI 0.18-0.95) after the first 6 months of follow-up, while increasing CRP (PFS: HR1.61, 95% CI 1.21-2.14; OS: HR2.04, 95% CI 1.51-2.74) and NLR (PFS: HR 1.57, 95% CI 1.29-1.91; OS: HR 1.63, 95% CI 1.35-1.97) were predictors of poor short-term prognosis.
Radiotherapy may be of importance to achieve a long-lasting response to immunotherapy, while indicators of systemic inflammation can help in identifying patients with poor short-term prognosis.
免疫检查点抑制剂（ICI）在晚期非小细胞肺癌（NSCLC）的标准治疗中的应用改善了这组患者的预后。然而，长期生存的情况仍然很少见。本研究的目的是确定反应的预测因素，特别是研究放射治疗对反应持续时间的影响。
对 78 例接受 ICI 作为晚期 NSCLC 二线治疗的患者，使用 Cox 回归分析研究了治疗前患者/肿瘤特征与无进展生存期（PFS）、总生存期（OS）和肺癌特异性生存期之间的关系。由于存在竞争风险，通过累积发生率图还检查了特定原因的死亡情况。
中位 OS 为 12.6 个月（95%CI 7.8-18.2），中位 PFS 为 4.1 个月（95%CI 3.0-6.2），中位随访时间为 49.7 个月（范围 20.9-51.5）。CRP 和中性粒细胞/淋巴细胞比值（NLR）的增加与较差的 PFS（CRP：HR 1.49，95%CI 1.12-1.98；NLR：HR 1.59，95%CI 1.22-1.85）和 OS（CRP：HR 1.94，95%CI 1.47-2.56；NLR：HR 1.54，95%CI 1.27-1.87）相关。免疫治疗前的放射治疗与患者预后无显著相关性。然而，当数据集在随访 6 个月时进行分割，以能够识别早期和晚期预后的预测因素时，我们发现，在接受免疫治疗前 6 个月内接受放射治疗的患者，在随访的前 6 个月后具有更好的 PFS（HR：0.27，95%CI 0.09-0.84）和肺癌特异性生存期（HR：0.41，95%CI 0.18-0.95），而 CRP（PFS：HR1.61，95%CI 1.21-2.14；OS：HR2.04，95%CI 1.51-2.74）和 NLR（PFS：HR 1.57，95%CI 1.29-1.91；OS：HR 1.63，95%CI 1.35-1.97）的增加是短期预后不良的预测因素。
放射治疗可能对实现免疫治疗的长期反应很重要，而全身炎症指标有助于识别短期预后不良的患者。
