Programmed Death-ligand 1 Expression In Patients Research Articles

Texture Features of 18F-Fluorodeoxyglucose Positron Emission Tomography for Predicting Programmed Death-Ligand-1 Levels in Non-Small Cell Lung Cancer.

Background: Identifying programmed death-ligand-1 (PD-L1) expression is crucial for optimizing treatment strategies involving immune checkpoint inhibitors. However, the role of intratumoral metabolic heterogeneity specifically derived from 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) images in predicting PD-L1 expression in patients with newly diagnosed non-small cell lung cancer (NSCLC) remains unexplored. Here, we investigated the association between FDG PET texture features and PD-L1 expression by retrospectively analyzing the data of patients newly diagnosed with NSCLC who underwent FDG PET/CT scans and PD-L1 immunohistochemical staining before treatment. Methods: Patients were categorized based on their tumor proportion scores (TPSs) into negative-, low-, and high-PD-L1 expression groups. We computed the maximum standardized uptake value and 31 texture features for the primary tumor from PET images and compared differences in parameters among the groups. Results: Of the 83 patients, 12, 45, and 26 were assigned to the negative-, low-, and high-PD-L1 expression groups, respectively. Six specific texture features (low gray-level run emphasis, short-run low gray-level emphasis, long-run high gray-level emphasis, low gray-level zone emphasis, high gray-level zone emphasis, and short-zone low gray-level emphasis) helped distinguish among all possible combinations. Conclusions: Our findings revealed that FDG PET texture features are potential imaging biomarkers for predicting PD-L1 expression in patients newly diagnosed with NSCLC.

Association of PD-L1 expression with driver gene mutations and clinicopathological characteristics in non-small cell lung cancer: A real-world study of 10 441 patients.

Programmed death ligand-1 (PD-L1) expression is a well-known predictive biomarker of response to immune checkpoint blockade in non-small cell lung cancer (NSCLC). However, there is limited evidence of the relationship between PD-L1 expression, clinicopathological features, and their association with major driver mutations in NSCLC patients in Latin America. This retrospective study included patients from Argentina with advanced NSCLC, and centralized evaluation of PD-L1 expression concurrently with genomic alterations in the driver genes EGFR, ALK, ROS1, BRAF, and/or KRAS G12C in FFPE tissue samples. A total of 10 441 patients with advanced NSCLC were analyzed. Adenocarcinoma was the most frequent histological subtype (71.1%). PD-L1 expression was categorized as PD-L1 negative (45.1%), PD-L1 positive low-expression 1%-49% (32.3%), and PD-L1 positive high-expression ≥50% (22.6%). Notably, current smokers and males were more likely to have tumors with PD-L1 tumor proportion score (TPS) ≥50% and ≥ 80% expression, respectively (p < 0.001 and p = 0.013). Tumors with non-adenocarcinoma histology had a significantly higher median PD-L1 expression (p < 0.001). Additionally, PD-L1 in distant nodes was more likely ≥50% (OR 1.60 [95% CI: 1.14-2.25, p < 0.01]). In the multivariate analysis, EGFR-positive tumors were more commonly associated with PD-L1 low expression (OR 0.62 [95% CI: 0.51-0.75], p < 0.01), while ALK-positive tumors had a significant risk of being PD-L1 positive (OR 1.81 [95% CI: 1.30-2.52], p < 0.01). PD-L1 expression was associated with well-defined clinicopathological and genomic features. These findings provide a comprehensive view of the expression of PD-L1 in patients with advanced NSCLC in a large Latin American cohort.

Immunotherapy for advanced non-small cell lung cancer with negative programmed death-ligand 1 expression: a literature review.

Lung cancer, mainly non-small cell lung cancer (NSCLC), is a serious threat to human life. In particular, the prognosis for advanced patients is poor, with the 5-year survival rate being exceedingly low. In recent years, immune checkpoint inhibition has changed the pattern of the treatment of a variety of cancers, including lung cancer; however, not all patients can benefit from immunotherapy, and thus finding the right biomarkers is particularly important for guiding precise treatment. Programmed death-ligand 1 (PD-L1) expression is one of the most valuable biomarkers for predicting the efficacy of lung cancer immunotherapy. Several studies have confirmed that patients with high PD-L1 expression are more likely to benefit from immunotherapy, but there is a high proportion of people with negative PD-L1 expression constituting a patient population that cannot be ignored. This article reviews the distribution of PD-L1 expression, the methods for evaluating PD-L1, and the effectiveness of immunotherapy for advanced NSCLC with negative PD-L1 expression. We performed a literature review to identify relevant data published until September 2022. In order to organize related information, we searched for literature in PubMed; abstracts and reports published in the American Society of Clinical Oncology (ASCO), the European Society for Medical Oncology (ESMO), the World Conference on Lung Cancer (WCLC), and other congresses; and clinical trial information registered on ClinicalTrials.gov. Information on the distribution of PD-L1 expression, detection of PD-L1, and immunotherapy efficacy for NSCLC with negative PD-L1 expression was collated and reviewed. The incidence of PD-L1 expression in patients with stage IIIB/IV NSCLC is similar in all regions of the world, but PD-L1 expression level is associated with certain clinicopathological features. The expression of PD-L1 can be evaluated by various detecting methods. Some immunotherapy regimens have better efficacy than traditional chemotherapy in patients with negative PD-L1 expression. Patients with NSCLC and negative PD-L1 expression can receive better survival benefits under some immunotherapy types, and these may represent a better treatment option for this relatively small patient population.

A novel computer-assisted tool for 3D imaging of programmed death-ligand 1 expression in immunofluorescence-stained and optically cleared breast cancer specimens

BackgroundProgrammed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) are the two most common immune checkpoints targeted in triple-negative breast cancer (BC). Refining patient selection for immunotherapy is non-trivial and finding an appropriate digital pathology framework for spatial analysis of theranostic biomarkers for PD-1/PD-L1 inhibitors remains an unmet clinical need.MethodsWe describe a novel computer-assisted tool for three-dimensional (3D) imaging of PD-L1 expression in immunofluorescence-stained and optically cleared BC specimens (n = 20). The proposed 3D framework appeared to be feasible and showed a high overall agreement with traditional, clinical-grade two-dimensional (2D) staining techniques. Additionally, the results obtained for automated immune cell detection and analysis of PD-L1 expression were satisfactory.ResultsThe spatial distribution of PD-L1 expression was heterogeneous across various BC tissue layers in the 3D space. Notably, there were six cases (30%) wherein PD-L1 expression levels along different layers crossed the 1% threshold for admitting patients to PD-1/PD-L1 inhibitors. The average PD-L1 expression in 3D space was different from that of traditional immunohistochemistry (IHC) in eight cases (40%). Pending further standardization and optimization, we expect that our technology will become a valuable addition for assessing PD-L1 expression in patients with BC.ConclusionVia a single round of immunofluorescence imaging, our approach may provide a considerable improvement in patient stratification for cancer immunotherapy as compared with standard techniques.

Concordance among three programmed death-ligand 1 (PD-L1) scoring methods and their association with clinical outcomes of tislelizumab (TIS) monotherapy in esophageal squamous cell carcinoma (ESCC).

390 Background: Multiple scoring methods and cutoffs have been developed to evaluate tumor PD-L1 expression status in patients with ESCC, and PD-L1 expression level has been associated with the degree of response to anti-programmed cell death protein 1 (PD-1)/PD-L1 therapy. Here, we retrospectively investigated concordance between three PD-L1 scoring methods and their association with clinical outcomes in RATIONALE-302, a phase 3 study of the anti-PD-1 antibody TIS vs investigator-chosen chemotherapy (ICC) as second-line treatment for advanced unresectable/metastatic ESCC (NCT03430843). Methods: Patients enrolled in RATIONALE-302 with evaluable PD-L1 expression by the tumor area positivity (TAP) score (based on visual estimation of positive tumor cells [TCs] and tumor-associated immune cells [ICs]) using the VENTANA PD-L1 (SP263) assay were categorized at a 10% cutoff. Stained slides from those patients were rescored post hoc using both combined positive score (CPS; based on counting positive TCs and ICs) at cutoff 10 and TC (based on counting positive TCs only) score at a 1% cutoff, thresholds currently used in ESCC for anti-PD-(L)1 therapy. Concordance at these thresholds was investigated. Clinical efficacy (overall survival [OS]) for PD-L1 subgroups was assessed. Results: Of 512 pts enrolled, 364 had evaluable TAP scores (TIS, n=180; ICC, n=184), of whom 355 had evaluable post-hoc CPS and TC scores (TIS, n=175; ICC, n=180). TAP score and CPS showed high concordance in terms of overall percentage agreement (OPA; 90% [95% confidence interval (CI): 86, 93]) and Cohen’s Kappa (0.79 [95% CI: 0.72, 0.85]), while TAP and TC scores had lower concordance (OPA: 78% [95% CI: 73, 82]; Cohen’s Kappa: 0.56 [95% CI: 0.47, 0.64]). OS benefit with TIS vs ICC in PD-L1 subgroups defined by TAP, CPS, and TC score cutoffs were generally similar (Table). Conclusions: OS subgroup analysis showed comparable treatment effect by TAP score at 10% cutoff, CPS at cutoff 10, and TC score at 1% cutoff based on SP263 staining. TAP score and CPS at these cutoffs exhibited substantial concordance. The results indicate that the less time-consuming, visually estimated TAP score and CPS may be interchangeable for clinical measurement of PD-L1 expression in patients with ESCC. Clinical trial information: NCT03430843 . [Table: see text]

Prognostic Significance of PD-L1 Expression in Gastric Cancer Patients with Peritoneal Metastasis.

Recently, many studies have explored the relationship between the expression of programmed death ligand 1 (PD-L1) and prognosis in gastric cancer, but there is still controversy. Additionally, few studies have specifically investigated the expression of PD-L1 in patients with peritoneal metastasis. Immunohistochemistry was used to analyze the expression of PD-L1 in gastric cancer patients with peritoneal metastasis. The combined positive score (CPS) was calculated to evaluate the expression of PD-L1, and the clinicopathological data were analyzed to explore prognostic significance. In total, 147 gastric cancer patients with peritoneal metastasis were enrolled. The negative PD-L1 expression was defined as a CPS < 1, and high PD-L1 expression was defined as a CPS ≥ 10. PD-L1 expression with CPS ≥ 1 and CPS-negative was detected in 67 (45.58%) and 80 (54.42%) patients, respectively. High PD-L1 expression at PD-L1 CPS ≥ 10 was detected in 21(14.29%) patients. The median overall survival (OS) was 18.53 months in the CPS < 10 group and 27.00 months in the CPS ≥ 10 group; the OS difference between the two groups was significant (p = 0.015). Multivariate analysis demonstrated that a poor Eastern Cooperative Oncology Group performance score (ECOG PS) (p = 0.002) and severe peritoneal metastasis (p = 0.033) were significantly associated with poor survival, while palliative chemotherapy (p = 0.002) and high PD-L1 expression (p = 0.008) were independent and significantly favorable prognostic factors. Our study demonstrated that PD-L1 expression was widely presented in gastric cancer patients with peritoneal metastasis, while a CPS no less than 10 predicted better prognosis.

Evaluation of PD-L1 expression in recurrent nonmetastatic sacral chordomas - a retrospective study

Introduction/Objective. Chordomas are rare tumors of a notochordal origin. Wide surgical resection is recommended for treatment. However, it is associated with a high risk of morbidity and mortality. Additionally, these tumors are resistant to chemotherapy. Thus, targeted therapy is needed for the treatment of chordomas. Programmed death ligand 1 (PD-L1) is a promising target for cancer treatment. Here, we investigated PD-L1 expression in patients with chordoma in a single-center study. Methods. Formalin-fixed paraffin-embedded blocks were evaluated for immunohistochemical analysis to evaluate PD-L1 expression. Clinicopathological variables, such as sex, age, and follow-up data (recurrence and outcome), were retrospectively collected from the patients? medical records. Results. Ten patients diagnosed with sacral chordoma in a single institution between December 2015 and November 2021 were included in this study. The median patient age was 57 years and the median follow-up period was 40 months. The surgical margins were negative in all cases, without any preoperative medical treatment. Four of the ten patients showed PD-L1 positivity on immune cells. These patients showed local recurrence, without metastasis. In these cases, the median time to local recurrence was 15 months. All the patients with the disease were alive. Conclusion. This study demonstrated that PD-L1 positivity in immune cells can be used as a predictive marker for local recurrence at the time of surgical treatment. This can potentially be used to determine the necessity to administer immunotherapy.

The impact of tertiary lymphoid structures on clinicopathological, genetic and gene expression characteristics in lung adenocarcinoma

IntroductionTertiary lymphoid structures (TLS) are observed in several cancers and are associated with favorable prognosis. This study aimed to examine the clinicopathological, genetic, and gene expression profiles of lung adenocarcinoma patients with TLS. MethodsA total of 112 patients with pathological stage IB lung adenocarcinoma who underwent complete resection between 2011 and 2015 were enrolled in this study. We investigated whether TLS correlated with prognosis and programmed death-ligand 1 (PD-L1) expression. Furthermore, the correlation of TLS with tumor mutation burden (TMB) and genetic mutations was evaluated in patients for whom whole-exon sequencing data were available. In addition, using the Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) dataset, gene expression analysis according to the TLS status was performed. ResultsAmong the 112 patients, 49 were TLS-positive (TLS+). TLS+ correlated with longer recurrence-free survival (RFS) than TLS-negative cases (TLS−) (hazard ratio [HR], 0.47; 95 % confidence interval [CI]: 0.23–0.88, p = 0.02). In the multivariate analysis, TLS was a better independent prognostic factor for RFS (HR 0.37, 95 %CI 0.18–0.72, p < 0.01). PD-L1 expression was not significantly different between TLS+ and TLS− patients (p = 0.54). TMB in TLS+ was similar to that in TLS− patients (p = 0.39); however, it tended to be lower than that in TLS− especially among smokers (p = 0.07). In gene expression analysis, RNA expression of chemokines related to lymph node formation, such as CXCL13, CCL19 and CCL21, was significantly higher, and biological processes such as positive regulation of humoral immune response and regulation of antigen receptor-mediated signaling pathway were enhanced in TLS+. ConclusionsTLS was a favorable prognostic factor and was not associated with PD-L1 expression in patients with lung adenocarcainoma. Moreover, gene expression analysis indicated that TLS is a site for the generation and regulation of antitumor immune responses.

Helicobacter pylori infection and PD-L1 expression in gastric cancer: A meta-analysis.

High expression of programmed death ligand-1 (PD-L1) has been related to good response to immunotherapy patients with gastric cancer (GC). However, the influence of Helicobacter pylori (HP) infection on PD-L1 expression in GC remains unknown. A meta-analysis was performed to evaluate the association between HP infection and PD-L1 expression in GC. Observational studies that investigated the relationship between HP infection and PD-L1 expression in patients with GC were obtained by search electronic databases, including PubMed, Embase, Cochrane's Library and Web of Science. A random-effect model incorporating the possible influence of between-study heterogeneity was used to pool the results. Ten studies with 1870 patients with GC contributed to the meta-analysis. Pooled results showed that HP infection was significantly associated with the tumour expression of PD-L1 (odds ratio [OR]: 1.90, 95% confidence interval: 1.33-2.72, p < .001; I2 =53%). Subgroup analyses showed that the association between HP infection and PD-L1 expression in GC was not significantly affected by sample size, methods for PD-L1 evaluation and quality score (p for subgroup analyses all >.05). However, a stronger association was observed in studies with higher prevalence of HP infection (≥35%, OR: 2.58) as compared with those with lower prevalence (<35%, OR: 1.45, p for subgroup difference=.04). Helicobacter pylori infection in GC patients is associated with tumour expression of PD-L1, suggesting HP infection may be a predictor of good response to immunotherapy in GC.

The prognostic significance of PD-L1 expression in patients with glioblastoma: A meta-analysis.

BackgroundGlioblastoma (GBM) is a malignant brain tumor associated with high morbidity and mortality rates with a poor prognosis. In recent years, studies on prognostic markers such as programmed death ligand 1 (PD-L1) have increased; however, their conclusions remain controversial. Here, relevant literature was reviewed and a meta-analysis was performed to clarify the correlation between PD-L1 expression and overall survival (OS) in GBM.MethodsThe non-foundational literature on PD-L1 expression associated with OS in GBM up to February 2022 was searched in the PubMed, Metstr, Cochrane, and Web of Science databases. Literature was rigorously screened according to inclusion and exclusion criteria, the total hazard ratio (HR), and corresponding 95% confidence intervals (CIs).ResultsCalculating the combined HR value and corresponding 95% CI of HR=1.124 (95% CI: 1.047–1.201, P=0.000, I2 (I-squared)=48.8%), it was shown that PD-L1 expression was significantly associated with low OS in GBM patients. Although I2 = 48.8% < 50%, to make the results more credible, in the cutoff values ≥10% subgroup HR=1.37 (95% CI: 1.07–1.67, P=0.000, I2 = 0%), which was also the result found in the first meta-analysis. In contrast, in the cutoff value ≥5% subgroup HR=1.14 (95% CI: 0.98–1.30, P=0.000, I2 = 59.8%) and in the cutoff value median PD-L1 expression levels subgroup HR=1.05 (95% CI: 0.92–1.18, P=0.000, I2 = 0%), indicating that PD-L1 expression was not associated with low OS in GBM. Furthermore, in four studies, we found no significant correlation between PD-L1 expression and the progression-free survival of GBM (HR=1.14, 95% CI:0.40–1.88, P=0.03, I2 = 29.3%).ConclusionPD-L1 expression was significantly associated with low OS in GBM patients; however, this result needs to be interpreted with caution and requires a large, multicenter clinical study in patients with similar baseline data for further evaluation.

MO19-3 PD-L1 expression in patients with HER2-negative advanced breast cancer: A multicenter retrospective study

Programmed death-ligand 1 (PD-L1) overexpression was seen in about 40% of triple-negative advanced breast cancer (TN-ABC) patients (pts). However, PD-L1 status in HER2-negative (HER2-ve) ABC pts is poorly understood, and no biomarker related to chemotherapy (CT) for HER2-ve ABC pts excluding PD-L1 in TN-ABC has been clarified. We evaluated PD-L1 status using SP142 and explored biomarkers for first-line (1L) paclitaxel + bevacizumab (PB) therapy using immune signatures in HER2-ve ABC pts.

Programmed Death Ligand-1 Expression Is Associated With Poorer Survival in Anal Squamous Cell Carcinoma.

Upregulation of programmed death ligand-1 (PD-L1), an immunoregulatory protein, is associated with an adverse outcome in several malignancies. Very few studies have evaluated PD-L1 expression in invasive anal squamous cell carcinoma (ASCC). To assess PD-L1 expression in patients with ASCC and correlate it with clinicopathologic factors and clinical outcomes. Fifty-one cases of ASCC were immunostained for PD-L1. PD-L1 expression by combined positive score and tumor proportion score was correlated with age, sex, HIV status, HIV viral load, CD4 count, stage, and outcomes. Kaplan-Meier curves for overall survival were plotted and compared using the log-rank test. Cox regression analysis was performed to identify significant prognostic factors (2-tailed P < .05 was considered statistically significant). PD-L1 was positive in 24 of 51 cases (47%) by combined positive score and in 18 of 51 (35%) by tumor proportion score. The median cancer-specific survival and 5-year overall survival were significantly lower in PD-L1+ patients. Age, sex, HIV status, HIV viral load, stage, and cancer progression were not significantly different between the 2 groups. CD4 count of more than 200/μL was significantly higher in PD-L1+ patients. PD-L1+ status remained statistically significant for worse overall survival on multivariate analysis. PD-L1+ status is an independent adverse prognostic factor for overall survival in ASCC. This study highlights the potential of PD-L1 targeted therapy in better management of ASCC.

Immunohistochemical expression of programmed death-ligand 1 and CD8 in glioblastomas

BackgroundGlioblastoma is the most aggressive primary malignant brain tumor in adults and is characterized by poor prognosis. Immune evasion occurs via programmed death-ligand 1 (PD-L1)/programmed death receptor 1 (PD-1) interaction. Some malignant tumors have responded to PD-L1/PD-1 blockade treatment strategies, and PD-L1 has been described as a potential predictive biomarker. This study discussed the expression of PD-L1 and CD8 in glioblastomas.MethodsThirty cases of glioblastoma were stained immunohistochemically for PD-L1 and CD8, where PD-L1 expression in glioblastoma tumor tissue above 1% is considered positive and CD-8 is expressed in tumor infiltrating lymphocytes. The expression of each marker was correlated with clinicopathologic parameters. Survival analysis was conducted to correlate progression-free survival (PFS) and overall survival (OS) with PD-L1 and CD8 expression.ResultsDiffuse/fibrillary PD-L1 was expressed in all cases (mean expression, 57.6%), whereas membranous PD-L1 was expressed in six of 30 cases. CD8-positive tumor-infiltrating lymphocytes (CD8+ TILs) had a median expression of 10%. PD-L1 and CD8 were positively correlated (p = .001). High PD-L1 expression was associated with worse PFS and OS (p = .026 and p = .001, respectively). Correlation of CD8+ TILs percentage with age, sex, tumor site, laterality, and outcomes were statistically insignificant. Multivariate analysis revealed that PD-L1 was the only independent factor that affected prognosis.ConclusionsPD-L1 expression in patients with glioblastoma is robust; higher PD-L1 expression is associated with lower CD8+ TIL expression and worse prognosis.

The Prognostic Values of HPV Genotypes and Tumor PD-L1 Expression in Patients With HPV-associated Endocervical Adenocarcinoma.

Despite the well-established pathogenic effect of high-risk human papillomavirus (hrHPV) genotypes on endocervical adenocarcinomas (ECAs), the prognostic values of hrHPV genotypes and their association with other prognostic variables have not been established. We categorized 120 usual-type human papillomavirus–associated (HPVA) ECA cases into 3 species groups (HPV16+, HPV18/45+, and other genotypes+) based on the hrHPV status. The clinical-stage, invasion patterns (Silva), and programmed death ligand-1 (PD-L1) expression were compared among genotype groups. In addition, log-rank test and Kaplan-Meier survival curves were used to compare progression-free survival (PFS) among different patient groups. A total of 120 ECA cases with positive hrHPV tests were included in this study. Among them, 51 (42.5%) were positive for HPV16, 50 (41.7%) were positive for HPV18 or 18/45, 9 (7.5%) were positive for other hrHPV genotypes (not including HPV16/18/45). Our data showed patients had no significant difference in clinical stages (P=0.51), invasion patterns (P=0.55), and PFS (P=0.59) across genotype groups. Overall, a relatively high prevalence of PD-L1 expression was observed in HPVA ECAs (25% by tumor proportion score [TPS] and 55% by a combined positive score [CPS]). Using TPS, 19.6% (10/51) HPV16+ cases, 32.0% (16/50) cases of HPV18 or 18/45+ cases, and 22.2% (2/9) cases of other genotypes+ cases demonstrated PD-L1 positivity. No significant difference in PD-L1 expression was seen across genotype groups (P=0.35). PD-L1 expression in tumors with patterns B and C was significantly higher than in those with pattern A (P=0.00002). Patients with PD-L1-positive tumors by either CPS or TPS showed significantly poorer PFS than those with PD-L1-negative tumors (CPS, P=0.025; TPS, P=0.001). Our data support that HPV genotypes have no prognostic value in HPVA ECAs, while PD-L1 expression serves as a negative prognostic marker in HPVA ECAs and implies an unfavorable outcome.

Prognostic significance of volume-based 18F-FDG PET/CT parameters and correlation with PD-L1 expression in patients with surgically resected lung adenocarcinoma.

The aim of this study was to retrospectively analyze 18F-FDG positron emission tomography/computed tomography (18F-FDG PET/CT) metabolic variables, programmed death-ligand 1 (PD-L1) and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) tumor expression, and other factors as predictors of disease-free survival (DFS) in patients with lung adenocarcinoma (LUAD) (stage IA–IIIA) who underwent surgical resection. We still lack predictor of immune checkpoint (programmed cell death-1 [PD-1]/PD-L1) inhibitors. Herein, we investigated the correlation between metabolic parameters from 18F-FDG PET/CT and PD-L1 expression in patients with surgically resected LUAD.Seventy-four patients who underwent 18F-FDG PET/CT prior to treatment were consecutively enrolled. The main 18F-FDG PET/CT-derived variables were primary tumor maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Surgical tumor specimens were analyzed for PD-L1 and p-STAT3 expression using immunohistochemistry. Correlations between immunohistochemistry results and 18F-FDG PET/CT-derived variables were compared. Associations of PD-L1 and p-STAT3 tumor expression, 18F-FDG PET/CT-derived variables, and other factors with DFS in resected LUAD were evaluated.All tumors were FDG-avid. The cutoff values of low and high SUVmax, MTV, and TLG were 12.60, 14.87, and 90.85, respectively. The results indicated that TNM stage, PD-L1 positivity, and high 18F-FDG PET/CT metabolic volume parameters (TLG ≥90.85 or MTV ≥14.87) were independent predictors of worse DFS in resected LUAD. No 18F-FDG metabolic parameters associated with PD-L1 expression were observed (chi-square test), but we found that patients with positive PD-L1 expression have significantly higher SUVmax (P = .01), MTV (P = .00), and TLG (P = .00) than patients with negative PD-L1 expression.18F-FDG PET/CT metabolic volume parameters (TLG ≥90.85 or MTV ≥14.87) were more helpful in prognostication than the conventional parameter (SUVmax), PD-L1 expression was an independent predictor of DFS in patients with resected LUAD. Metabolic parameters on 18F-FDG PET/CT have a potential role for 18F-FDG PET/CT in selecting candidate LUAD for treatment with checkpoint inhibitors.

Quantitative CT texture analysis in predicting PD-L1 expression in locally advanced or metastatic NSCLC patients

PurposeThe assessment of Programmed death-ligand 1 (PD-L1) expression has become a game changer in the treatment of patients with advanced non-small cell lung cancer (NSCLC). We aimed to investigate the ability of Radiomics applied to computed tomography (CT) in predicting PD-L1 expression in patients with advanced NSCLC.MethodsBy applying texture analysis, we retrospectively analyzed 72 patients with advanced NSCLC. The datasets were randomly split into a training cohort (2/3) and a validation cohort (1/3). Forty radiomic features were extracted by manually drawing tumor volumes of interest (VOIs) on baseline contrast-enhanced CT. After selecting features on the training cohort, two predictive models were created using binary logistic regression, one for PD-L1 values ≥ 50% and the other for values between 1 and 49%. The two models were analyzed with ROC curves and tested in the validation cohort.ResultsThe Radiomic Score (Rad-Score) for PD-L1 values ≥ 50%, which consisted of Skewness and Low Gray-Level Zone Emphasis (GLZLM_LGZE), presented a cut-off value of − 0.745 with an area under the curve (AUC) of 0.811 and 0.789 in the training and validation cohort, respectively. The Rad-Score for PD-L1 values between 1 and 49% consisted of Sphericity, Skewness, Conv_Q3 and Gray Level Non-Uniformity (GLZLM_GLNU), showing a cut-off value of 0.111 with AUC of 0.763 and 0.806 in the two population, respectively.ConclusionRad-Scores obtained from CT texture analysis could be useful for predicting PD-L1 expression and guiding the therapeutic choice in patients with advanced NSCLC.

CT-Based Hand-crafted Radiomic Signatures Can Predict PD-L1 Expression Levels in Non-small Cell Lung Cancer: a Two-Center Study.

Here, we used pre-treatment CT images to develop and evaluate a radiomic signature that can predict the expression of programmed death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC). We then verified its predictive performance by cross-referencing its results with clinical characteristics. This two-center retrospective analysis included 125 patients with histologically confirmed NSCLC. A total of 1287 hand-crafted radiomic features were observed from manually determined tumor regions. Valuable features were then selected with a ridge regression-based recursive feature elimination approach. Machine learning-based prediction models were then built from this and compared each other. The final radiomic signature was built using logistic regression in the primary cohort, and then tested in a validation cohort. Finally, we compared the efficacy of the radiomic signature to the clinical model and the radiomic-clinical nomogram. Among the 125 patients, 89 were classified as having PD-L1 positive expression. However, there was no significant difference in PD-L1 expression levels determined by clinical characteristics (P = 0.109-0.955). Upon selecting 9 radiomic features, we found that the logistic regression-based prediction model performed the best (AUC = 0.96, P < 0.001). In the external cohort, our radiomic signature showed an AUC of 0.85, which outperformed both the clinical model (AUC = 0.38, P < 0.001) and the radiomics-nomogram model (AUC = 0.61, P < 0.001). Our CT-based hand-crafted radiomic signature model can effectively predict PD-L1 expression levels, providing a noninvasive means of better understanding PD-L1 expression in patients with NSCLC.

The detection value of PD-L1 expression in biopsy specimens and surgical resection specimens in non-small cell lung cancer: a meta-analysis.

BackgroundThe detection value of different types of specimens for programmed death ligand-1 (PD-L1) expression remains controversial. As such, the purpose of this meta-analysis was to compare the detection value of biopsy specimens and surgical resection specimens for PD-L1 expression in patients with non-small cell lung cancer (NSCLC).MethodsPubMed and Web of Science were searched prior to December 2020 to identify studies that compared the detection value of biopsy specimens and surgical resection specimens for PD-L1 expression in NSCLC. Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 scale was used to evaluate the quality of the literature included. The detection value of different types of specimens for PD-L1 expression was then assessed. Besides, the relative risk (RR) with 95% CI were pooled using Review Manager 5.3 software and Stata 14.0 software.ResultsThe meta-analysis involved 12 articles and included 877 patients. There was no significant difference in the detection rate of PD-L1 at the 1% cutoff between biopsy specimens and surgical resection specimens (RR =0.89, 95% CI: 0.70–1.12, P=0.33). However, there was a significant difference between two groups when the cutoff is 50% (RR =0.69, 95% CI: 0.58–0.83, P<0.01). In addition, a subgroup analysis of the type of biopsy specimens and the PD-L1 qualitative immunohistochemistry (IHC) assays showed that the detection rate of PD-L1 in small biopsies and using the SP142 antibody were lower than in surgical specimens and using other antibodies for both the 1% and 50% cut-offs (P<0.01).ConclusionsCurrent evidence suggests that caution must be taken when using biopsy specimens from patients with advanced NSCLC to evaluate PD-L1 status eligible for immunotherapy, additional biopsy specimens sampling may be needed to minimize the risk of tumor misclassification. In addition, PD-L1 qualitative IHC assays and the type of biopsy specimens related to PD-L1 expression detection.

Analyses of PD-L1 and Inflammatory Gene Expression Association with Efficacy of Nivolumab ± Ipilimumab in Gastric Cancer/Gastroesophageal Junction Cancer

In advanced gastric cancer/gastroesophageal junction cancer (GC/GEJC), there is a need to identify biomarkers of response to therapies, such as immune checkpoint inhibitors. In post hoc exploratory analyses from CheckMate 032 (GC/GEJC cohort), we evaluated associations between nivolumab ± ipilimumab (NIVO ± IPI) efficacy and programmed death ligand 1 (PD-L1) expression, defined by tumor cells (% TC) or combined positive score (CPS; sum of PD-L1-staining TCs + immune cells, divided by total viable TCs, × 100) using the Dako PD-L1 IHC 28-8 pharmDx assay, or inflammatory gene expression. There was a trend toward increased efficacy (objective response and overall survival) when PD-L1 expression was determined by CPS compared with % TC at higher cutoffs of ≥5 and ≥10 in the pooled analysis of all treatment regimens. In this analysis, 19% and 26% of patients with PD-L1-positive tumors at a CPS cutoff of ≥5 and ≥10, respectively, had an objective response compared with 8% and 9% of patients at the equivalent % TC cutoffs. Longer survival was demonstrated in patients with PD-L1-positive (defined by CPS cutoffs of ≥5 and ≥10) versus PD-L1-negative status. Similar results were observed in the NIVO 1 mg/kg + IPI 3 mg/kg subgroup. Multiple inflammatory gene signatures/transcripts, including a signature consisting of four genes (CD274, CD8A, LAG3, and STAT1), showed associations with response to NIVO ± IPI. This study suggests a greater association of PD-L1 expression by CPS with NIVO ± IPI efficacy compared with % TC PD-L1 expression in patients with GC/GEJC. Inflammatory signatures were also associated with NIVO ± IPI response, warranting further investigation.See related commentary by Moutafi and Rimm, p. 3812.

Impact of Metabolic Activity in Hepatocellular Carcinoma: Association With Immune Status and Vascular Formation.

We evaluated the prognostic value of fluorine‐18 fluorodeoxyglucose (18F‐FDG) positron emission tomography/computed tomography (PET/CT) in hepatocellular carcinoma (HCC). Their association with programmed death ligand 1 (PD‐L1) expression and vascular formation was further investigated. In this retrospective study, using a database of 418 patients who had undergone 18F‐FDG PET/CT before hepatic resection for HCC, immunohistochemical staining of PD‐L1, clusters of differentiation (CD) 8, CD68, and CD34 was performed. Patients with a high maximum standardized uptake value (SUVmax) on 18F‐FDG PET/CT showed a significantly worse recurrence‐free survival (RFS) (hazard ratio [HR]: 1.500; 95% confidence interval [CI]: 1.088‐2.069; P = 0.0133) and overall survival (OS) (HR: 2.259; 95% CI: 1.276‐4.000; P = 0.0052) than patients with a low SUVmax. Logistic regression analysis showed that a high SUVmax in HCC was significantly associated with PD‐L1‐positive expression (odds ratio: 4.407; 95% CI: 2.265‐8.575; P < 0.0001). SUVmax values of HCC were associated with intratumoral CD8‐positive T‐cell counts (P = 0.0044) and CD68‐positive macrophage counts (P = 0.0061). Stratification based on SUVmax, PD‐L1 expression, and the vessels that encapsulate tumor clusters (VETC) status was also significantly associated with RFS and OS. SUVmax, VETC, and PDL1 expression were independently predictive of survival on multivariable analysis. Conclusion: Our large cohort study showed that a high SUVmax on 18F‐FDG PET/CT is associated with a poor clinical outcome and PD‐L1 expression in patients with HCC. Additionally, stratification of patients based on the combination of SUVmax, PD‐L1 expression, and the VETC status predicts poor clinical outcome.