Kim Sungjin, Lee Jeonghyo, Chung Jin-Haeng
Department of Translational Medicine, Seoul National University College of Medicine, Seoul, Korea.
Department of Pathology and Translational Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Cancer Res Treat. 2025 Apr;57(2):401-411. doi: 10.4143/crt.2024.670. Epub 2024 Sep 9.
Major pathologic response (MPR), defined as ≤ 10% of residual viable tumor (VT), is a prognostic factor in non-small cell lung cancer (NSCLC) after neoadjuvant therapy. This study evaluated interobserver reproducibility in assessing MPR, compared area-weighted and unweighted VT (%) calculation, and determined optimal VT (%) cutoffs across histologic subtypes for survival prediction.
This retrospective study included 108 patients with NSCLC who underwent surgical resection after neoadjuvant chemotherapy or chemoradiation at Seoul National University Bundang Hospital between 2009-2018. Three observers with varying expertise independently assessed tumor bed and VT (%) based on digital whole-slide images.
Reproducibility in tumor bed delineation was reduced in squamous cell carcinoma (SqCC) with smaller tumor bed, although overall concordance was high (Dice coefficient, 0.96; intersection-over-union score, 0.92). Excellent agreement was achieved for VT (%) (intraclass correlation coefficient=0.959) and MPR using 10% cutoff (Fleiss' kappa=0.911). Shifting between area-weighted and unweighted VT (%) showed only one case differing in MPR status out of 81 cases. The optimal cutoff was 10% for both adenocarcinoma (ADC) and SqCC. MPR+ was observed in 18 patients (17%), with SqCC showing higher MPR+ rates (p=0.044), lower VT (%) (p < 0.001), and better event-free survival (p=0.015) than ADC. MPR+ significantly improved overall survival (p=0.023), event-free survival (p=0.001), and lung cancer-specific survival (p=0.012).
While MPR assessment demonstrated robust reproducibility with minimal impact from the tumor bed, attention is warranted when evaluating smaller tumor beds in SqCC. A 10% cutoff reliably predicted survival across histologic subtypes with higher interobserver reproducibility.
主要病理缓解（MPR）定义为残余存活肿瘤（VT）≤10%，是新辅助治疗后非小细胞肺癌（NSCLC）的一个预后因素。本研究评估了评估MPR时观察者间的可重复性，比较了面积加权和未加权的VT（%）计算，并确定了不同组织学亚型用于生存预测的最佳VT（%）临界值。
本回顾性研究纳入了2009年至2018年间在首尔国立大学盆唐医院接受新辅助化疗或放化疗后接受手术切除的108例NSCLC患者。三名专业水平不同的观察者基于数字全切片图像独立评估肿瘤床和VT（%）。
鳞状细胞癌（SqCC）中肿瘤床较小，肿瘤床描绘的可重复性降低，尽管总体一致性较高（Dice系数，0.96；交并比评分，0.92）。VT（%）（组内相关系数=0.959）和使用10%临界值的MPR（Fleiss'kappa=0.911）达成了极佳的一致性。在81例病例中，面积加权和未加权的VT（%）之间的转换仅显示1例MPR状态不同。腺癌（ADC）和SqCC的最佳临界值均为10%。18例患者（17%）观察到MPR+，SqCC的MPR+率更高（p=0.044），VT（%）更低（p<0.001），无事件生存期优于ADC（p=0.015）。MPR+显著改善了总生存期（p=0.023）、无事件生存期（p=0.001）和肺癌特异性生存期（p=0.012）。
虽然MPR评估显示出强大的可重复性且受肿瘤床影响最小，但在评估SqCC中较小的肿瘤床时仍需谨慎。10%的临界值能可靠地预测不同组织学亚型的生存情况，且观察者间的可重复性更高。
