Kudura Ken, Ritz Nando, Templeton Arnoud J, Kutzker Tim, Foerster Robert, Antwi Kwadwo, Kreissl Michael C, Hoffmann Martin H K
Department of Nuclear Medicine, Sankt Clara Hospital, 4058 Basel, Switzerland.
Department of Radiology, Sankt Clara Hospital, 4058 Basel, Switzerland.
J Clin Med. 2023 May 28;12(11):3725. doi: 10.3390/jcm12113725.
We aimed to assess the predictive value of the total metabolic tumor burden prior to treatment in patients with advanced non-small-cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICIs).
Pre-treatment 2-deoxy-2-[F]fluoro-D-glucose positron emission tomography/computed tomography (PET/CT) scans performed in two consecutive years for staging in adult patients with confirmed NSCLC were considered. Volume, maximum/mean standardized uptake value (SUVmax/SUVmean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were assessed per delineated malignant lesion (including primary tumor, regional lymph nodes and distant metastases) in addition to the morphology of the primary tumor and clinical data. Total metabolic tumor burden was captured by MTV and TLG. Overall survival (OS), progression-free survival (PFS) and clinical benefit (CB) were used as endpoints for response to treatment.
A total of 125 NSCLC patients were included. Osseous metastases were the most frequent distant metastases (n = 17), followed by thoracal distant metastases (pulmonal = 14 and pleural = 13). Total metabolic tumor burden prior to treatment was significantly higher in patients treated with ICIs (mean MTV ± standard deviation (SD) 72.2 ± 78.7; mean TLG ± SD 462.2 ± 538.9) compared to those without ICI treatment (mean MTV ± SD 58.1 ± 233.8; mean TLG ± SD 290.0 ± 784.2). Among the patients who received ICIs, a solid morphology of the primary tumor on imaging prior to treatment was the strongest outcome predictor for OS (Hazard ratio HR 28.04, < 0.01), PFS (HR 30.89, < 0.01) and CB (parameter estimation PE 3.46, < 0.01), followed by the metabolic features of the primary tumor. Interestingly, total metabolic tumor burden prior to immunotherapy showed a negligible impact on OS ( = 0.04) and PFS ( = 0.01) after treatment given the hazard ratios of 1.00, but also on CB ( = 0.01) given the PE < 0.01. Overall, biomarkers on pre-treatment PET/CT scans showed greater predictive power in patients receiving ICIs, compared to patients without ICI treatment.
Morphological and metabolic properties of the primary tumors prior to treatment in advanced NSCLC patients treated with ICI showed great outcome prediction performances, as opposed to the pre-treatment total metabolic tumor burdens, captured by MTV and TLG, both with negligible impact on OS, PFS and CB. However, the outcome prediction performance of the total metabolic tumor burden might be influenced by the value itself (e.g., poorer prediction performance at very high or very low values of total metabolic tumor burden). Further studies including subgroup analysis with regards to different values of total metabolic tumor burden and their respective outcome prediction performances might be needed.
我们旨在评估接受免疫检查点抑制剂（ICI）治疗的晚期非小细胞肺癌（NSCLC）患者治疗前的总代谢肿瘤负荷的预测价值。
考虑对连续两年进行的用于确诊NSCLC成年患者分期的治疗前2-脱氧-2-[F]氟代-D-葡萄糖正电子发射断层扫描/计算机断层扫描（PET/CT）进行分析。除了原发性肿瘤的形态和临床数据外，还对每个划定的恶性病变（包括原发性肿瘤、区域淋巴结和远处转移灶）评估其体积、最大/平均标准化摄取值（SUVmax/SUVmean）、代谢肿瘤体积（MTV）和总病变糖酵解（TLG）。通过MTV和TLG来获取总代谢肿瘤负荷。总生存（OS）、无进展生存（PFS）和临床获益（CB）用作治疗反应的终点。
共纳入125例NSCLC患者。骨转移是最常见的远处转移（n = 17），其次是胸部远处转移（肺部 = 14例，胸膜 = 13例）。接受ICI治疗的患者治疗前的总代谢肿瘤负荷显著高于未接受ICI治疗的患者（平均MTV±标准差（SD）72.2±78.7；平均TLG±SD 462.2±538.9）（平均MTV±SD 58.1±233.8；平均TLG±SD 290.0±784.2）。在接受ICI治疗的患者中，治疗前影像学上原发性肿瘤的实体形态是OS（风险比HR 28.04，P<0.01）、PFS（HR 30.89，P<0.01）和CB（参数估计PE 3.46，P<0.01）的最强结果预测因素，其次是原发性肿瘤的代谢特征。有趣的是，鉴于风险比为1.00，免疫治疗前的总代谢肿瘤负荷对治疗后的OS（P = 0.04）和PFS（P = 0.01）影响可忽略不计，但鉴于PE<0.01，对CB（P = 0.01）也有影响。总体而言，与未接受ICI治疗的患者相比，治疗前PET/CT扫描上的生物标志物在接受ICI治疗的患者中显示出更大的预测能力。
接受ICI治疗的晚期NSCLC患者治疗前原发性肿瘤的形态和代谢特性显示出良好的结果预测性能，与MTV和TLG所反映的治疗前总代谢肿瘤负荷相反，MTV和TLG对OS、PFS和CB的影响均可忽略不计。然而，总代谢肿瘤负荷的结果预测性能可能受其自身值的影响（例如，在总代谢肿瘤负荷非常高或非常低的值时预测性能较差）。可能需要进一步的研究，包括针对总代谢肿瘤负荷的不同值及其各自结果预测性能的亚组分析。
