Relationship between SP142 PD-L1 Expression and (18)F-FDG Uptake in Non-Small-Cell Lung Cancer.

Immune checkpoint blockers constitute the first-line treatment for advanced non-small-cell lung cancer (NSCLC) with ≥50% PD-L1 expression. In NSCLC, PD-L1 positivity is correlated with high 18F-fluorodeoxyglucose (18F-FDG) uptake. However, these studies only included patients undergoing surgical resection, almost all in their early stages. Moreover, differences in 18F-FDG uptake between NSCLC with high (≥50%) and low (49%) PD-L1 expression remain unknown. We aimed to investigate the association between metabolic parameter 18F-FDG uptake and PD-L1 expression status in NSCLC patients. From February 2017 to June 2018, 428 consecutive NSCLC patients who underwent 18F-FDG positron emission tomography/computed tomography (PET/CT) and SP142 PD-L1 expression analysis were retrospectively assessed. The association between clinicopathological characteristics and PD-L1 expression was examined. The frequency of PD-L1-positive tumors was 38.1% (163/428), 28.5% (91/319), and 64.2% (61/95) for NSCLC, adenocarcinoma (ADC), and squamous cell carcinoma (SCC), respectively. Maximal standard uptake (SUVmax) was significantly higher in PD-L1-positive than in PD-L1-negative NSCLC (p < 0.0001), ADC (p < 0.0001), and SCC (p=0.006). SUVmax was significantly higher in NSCLC (p=0.001) and ADC (p=0.003) with high rather than low PD-L1 expression. The receiver operating characteristic curve yielded area under the curve values of 0.726 (95% CI, 0.679-0.774, p < 0.0001), 0.694 (95% CI, 0.634-0.755, p < 0.0001), and 0.625 (95% CI, 0.513-0.738, p=0.044) for NSCLC, ADC, and SCC, respectively. 18F-FDG tumor uptake is strongly, positively correlated with PD-L1 expression in NSCLC and significantly differs between high and low PD-L1-expressing individuals.

Zhao L ，Liu J ，Shi J ，Wang H ... -  《-》

Metabolic characteristics of programmed cell death-ligand 1-expressing lung cancer on (18) F-fluorodeoxyglucose positron emission tomography/computed tomography.

Programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) have been identified as novel targets of immunotherapy of lung cancer. In present study, we evaluated the metabolic characteristics of lung cancer by using 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT) with regard to PD-L1 protein expression. PD-L1 protein expression was evaluated by immunohistochemistry with the antibody clone SP142 in 579 surgically resected primary lung cancer patients. Cases with less than 5% tumor membrane staining were considered negative. We examined the association between the frequency of PD-L1 protein expression and the maximum standardized uptake value (SUVmax) in preoperative 18 F-FDG PET/CT. The cut-off values for SUVmax were determined by receiver operating characteristic curve analyses. The SUVmax was significantly higher in nonsmall cell lung cancer (NSCLC) patients with PD-L1 protein expression compared with those without PD-L1 protein expression (P < 0.0001). However, there was no correlation between SUVmax and PD-L1 protein expression in patients with neuroendocrine tumors (P = 0.6545). Multivariate analysis revealed that smoking, the presence of pleural invasion, and high SUVmax were independent predictors of PD-L1 positivity. PD-L1-expressing NSCLC had a high glucose metabolism. The SUVmax in preoperative 18 F-FDG PET/CT was a predictor of PD-L1 protein expression in patients with NSCLC.

Takada K ，Toyokawa G ，Okamoto T ，Baba S ，Kozuma Y ，Matsubara T ，Haratake N ，Akamine T ，Takamori S ，Katsura M ，Shoji F ，Honda H ，Oda Y ，Maehara Y ... -  《Cancer Medicine》

Association between (18)F-FDG metabolic activity and programmed death ligand-1 (PD-L1) expression using 22C3 immunohistochemistry assays in non-small cell lung cancer (NSCLC) resection specimens.

Zhao L ，Liu J ，Wang H ，Shi J ... -  《-》

(18)F-FDG maximum standard uptake value predicts PD-L1 expression on tumor cells or tumor-infiltrating immune cells in non-small cell lung cancer.

Hu B ，Chen W ，Zhang Y ，Shi H ，Cheng D ，Xiu Y ... -  《-》

Predicting programmed death-ligand 1 (PD-L1) expression with fluorine-18 fluorodeoxyglucose ([(18)F]FDG) positron emission tomography/computed tomography (PET/CT) metabolic parameters in resectable non-small cell lung cancer.

Programmed death-ligand 1 (PD-L1) expression is a predictive biomarker for immunotherapy in non-small cell lung cancer (NSCLC). PD-L1 and glucose transporter 1 expression are closely associated, and studies demonstrate correlation of PD-L1 with glucose metabolism. The aim of this study was to investigate the association of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) metabolic parameters with PD-L1 expression in primary lung tumour and lymph node metastases in resected NSCLC. We conducted a retrospective analysis of 210 patients with node-positive resectable stage IIB-IIIB NSCLC. PD-L1 tumour proportion score (TPS) was determined using the DAKO 22C3 immunohistochemical assay. Semi-automated techniques were used to analyse pre-operative [18F]FDG-PET/CT images to determine primary and nodal metabolic parameter scores (including max, mean, peak and peak adjusted for lean body mass standardised uptake values (SUV), metabolic tumour volume (MTV), total lesional glycolysis (TLG) and SUV heterogeneity index (HISUV)). Patients were predominantly male (57%), median age 70 years with non-squamous NSCLC (68%). A majority had negative primary tumour PD-L1 (TPS < 1%; 53%). Mean SUVmax, SUVmean, SUVpeak and SULpeak values were significantly higher (p < 0.05) in those with TPS ≥ 1% in primary tumour (n = 210) or lymph nodes (n = 91). However, ROC analysis demonstrated only moderate separability at the 1% PD-L1 TPS threshold (AUCs 0.58-0.73). There was no association of MTV, TLG and HISUV with PD-L1 TPS. This study demonstrated the association of SUV-based [18F]FDG-PET/CT metabolic parameters with PD-L1 expression in primary tumour or lymph node metastasis in resectable NSCLC, but with poor sensitivity and specificity for predicting PD-L1 positivity ≥ 1%. Whilst SUV-based fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography metabolic parameters may not predict programmed death-ligand 1 positivity ≥ 1% in the primary tumour and lymph nodes of resectable non-small cell lung cancer independently, there is a clear association which warrants further investigation in prospective studies. Non-applicable KEY POINTS: • Programmed death-ligand 1 immunohistochemistry has a predictive role in non-small cell lung cancer immunotherapy; however, it is both heterogenous and dynamic. • SUV-based fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) metabolic parameters were significantly higher in primary tumour or lymph node metastases with positive programmed death-ligand 1 expression. • These SUV-based parameters could potentially play an additive role along with other multi-modal biomarkers in selecting patients within a predictive nomogram.

Hughes DJ ，Josephides E ，O'Shea R ，Manickavasagar T ，Horst C ，Hunter S ，Tanière P ，Nonaka D ，Van Hemelrijck M ，Spicer J ，Goh V ，Bille A ，Karapanagiotou E ，Cook GJR ... -  《-》