Baskent University Medical Faculty, Department of Radiation Oncology, Adana, Turkey.
Mersin City Hospital, Radiation Oncology Clinics, Mersin, Turkey.
PLoS One. 2019 Jul 22;14(7):e0218627. doi: 10.1371/journal.pone.0218627. eCollection 2019.
To investigate the detrimental effects of prolonged overall radiotherapy duration (ORTD) on survival outcomes of stage IIIB/C NSCLC patients treated with concurrent chemoradiotherapy (C-CRT).
The study cohort consisted of 956 patients who underwent C-CRT for stage IIIB/C NSCLC. Primary endpoint was the association between the ORTD and overall survival (OS) with locoregional progression-free survival (LRPFS) and PFS comprising the secondary endpoints. Receiver operating characteristic (ROC) curve analysis was utilized for accessibility of the cut-off that interacts with survival outcomes. Multivariate Cox model was utilized to identify the independent associates of survival outcomes.
The ROC curve analysis exhibited significance at 49 days of ORTD cut-off that dichotomized patients into ORTD<50 versus ORTD≥50 days groups for OS [area under the curve (AUC): 82.8%; sensitivity: 81.1%; specificity: 74.8%], LRPFS (AUC: 91.9%; sensitivity: 90.6%; specificity: 76.3%), and PFS (AUC: 76.1%; sensitivity: 72.4%; specificity: 68.2%), respectively. Accordingly, ORTD≥50 days group had significantly shorter median OS (P<0.001), LRPFS (P<0.001), and PFS (P<0.001); and 10-year actuarial locoregional control (P<0.001) and distant metastases-free (P<0.011) rates than the ORTD<50 days group. The ORTD retained its significant association with survival outcomes at multivariate analyses independent of the other favorable covariates (p<0.001, for OS, LRPFS, and PFS): Stage IIIB disease (versus IIIC), lymph node bulk <2 cm (versus ≥2 cm), and 2-3 chemotherapy cycles (versus 1). The higher sensitivity for LRPFS (90.6%) than PFS (72.4%) on ROC curve analysis suggested the prolonged ORTD-induced decrements in locoregional control rates as the major cause of the poor survival outcomes.
Longer ORTD beyond ≥50 days was associated with significantly poorer OS, LRPFS and PFS outcomes, where reduced locoregional control rates appeared to be the main causative.
本研究旨在探讨总放疗时间(ORTD)延长对接受同期放化疗(C-CRT)治疗的 IIIB/C 期非小细胞肺癌(NSCLC)患者生存结局的不利影响。
该研究队列纳入了 956 例接受 C-CRT 治疗的 IIIB/C 期 NSCLC 患者。主要终点为 ORTD 与总生存(OS)以及局部区域无进展生存(LRPFS)和无进展生存(PFS)的相关性,次要终点包括 LRPFS 和 PFS。利用受试者工作特征(ROC)曲线分析确定与生存结局相关的截断值。采用多变量 Cox 模型确定生存结局的独立相关因素。
ROC 曲线分析显示,ORTD 截断值为 49 天时具有统计学意义,将患者分为 ORTD<50 天组和 ORTD≥50 天组,用于 OS [曲线下面积(AUC):82.8%;灵敏度:81.1%;特异性:74.8%]、LRPFS(AUC:91.9%;灵敏度:90.6%;特异性:76.3%)和 PFS(AUC:76.1%;灵敏度:72.4%;特异性:68.2%)。因此,ORTD≥50 天组的中位 OS(P<0.001)、LRPFS(P<0.001)和 PFS(P<0.001)均显著缩短,10 年局部区域控制率(P<0.001)和远处转移无进展率(P<0.011)也显著低于 ORTD<50 天组。多变量分析显示,ORTD 与 OS、LRPFS 和 PFS 等生存结局仍具有显著相关性,独立于其他有利的协变量(P<0.001):III B 期疾病(与 III C 期相比)、淋巴结肿大<2 cm(与≥2 cm 相比)和 2-3 个化疗周期(与 1 个周期相比)。ROC 曲线分析显示,LRPFS 的灵敏度(90.6%)高于 PFS(72.4%),提示延长 ORTD 导致局部区域控制率下降是导致生存结局较差的主要原因。
ORTD 延长至≥50 天与 OS、LRPFS 和 PFS 结局显著恶化相关,其中局部区域控制率降低似乎是主要原因。