Functional Engagement of the PD-1/PD-L1 Complex But Not PD-L1 Expression Is Highly Predictive of Patient Response to Immunotherapy in Non-Small-Cell Lung Cancer.

PURPOSE: In many cancers, the expression of immunomodulatory ligands leads to immunoevasion, as exemplified by the interaction of PD-L1 with PD-1 on tumor-infiltrating lymphocytes. Profound advances in cancer treatments have come with the advent of immunotherapies directed at blocking these immuno-suppressive ligand-receptor interactions. However, although there has been success in the use of these immune checkpoint interventions, correct patient stratification for these therapies has been challenging. MATERIALS AND METHODS: To address this issue of patient stratification, we have quantified the intercellular PD-1/PD-L1 interaction in formalin-fixed paraffin-embedded tumor samples from patients with non-small cell lung carcinoma, using a high-throughput automated quantitative imaging platform (quantitative functional proteomics [QF-Pro]). RESULTS: The multisite blinded analysis across a cohort of 188 immune checkpoint inhibitor-treated patients demonstrated the intra- and intertumoral heterogeneity of PD-1/PD-L1 immune checkpoint engagement and notably showed no correlation between the extent of PD-1/PD-L1 interaction and PD-L1 expression. Importantly, PD-L1 expression scores used clinically to stratify patients correlated poorly with overall survival; by contrast, patients showing a high PD-1/PD-L1 interaction had significantly better responses to anti-PD-1/PD-L1 treatments, as evidenced by increased overall survival. This relationship was particularly strong in the setting of first-line treatments. CONCLUSION: The functional readout of PD-1/PD-L1 interaction as a predictive biomarker for the stratification of patients with non-small-cell lung carcinoma, combined with PD-L1 expression, should significantly improve the response rates to immunotherapy. This would both capture patients excluded from checkpoint immunotherapy (high PD-1/PD-L1 interaction but low PD-L1 expression, 24% of patients) and additionally avoid treating patients who despite their high PD-L1 expression do not respond and suffer from side effects.

Complications and diagnostic accuracy of CT-guided 18G tru-cut versus end-cut percutaneous core needle biopsy of solitary solid lung nodules.

PURPOSE: Percutaneous biopsy has demonstrated high accuracy in diagnosis of lung nodules, but the technique is not innocuous and a yield decrease in lesions smaller than 20 mm has been reported. We carried out a prospective study to evaluate and compare the complications and efficacy of percutaneous core needle biopsy (CNB) of solitary solid lung nodules, which were performed with two types of automatic guns. METHODS: 330 consecutive CT-guided CNB were included. Tru-cut or end-cut 18G devices were used alternatively. Nodules were categorized by their size: ≤10 mm, 11-20 mm and >20 mm. Incidence of complications such as pneumothorax or hemoptysis and factors influencing them (nodule size and depth within lung parenchyma) were evaluated. Diagnostic accuracy of CNB achieved in the three groups of nodules regarding the two different needles were calculated and statistically evaluated and compared. RESULTS: We performed 68 CNB in nodules ≤10 mm, 130 in 11-20 mm and 132 in >20 mm. Pneumothorax appeared in 24.2% of them, but only 5.7% required drainage. Hemoptysis was developed in 9.4% and abundant hemoptysis with hypoxemia was observed in only 4.2% of patients. Regarding appearance of complications between the two needle types, no significant differences were found. A higher risk of hemoptysis was observed in nodules ≤10 mm (OR = 3.87; 95% CI = 1.24-12.06, P = 0.019) and in those located deeper in pulmonary parenchyma (OR = 2.21; 95% CI = 1.04-4.69, P = 0.038). End-cut needles reached a diagnostic accuracy of 93.7%, 92.1% and 98.3%, in nodules sized ≤10 mm, 11-20 mm and >20 mm, respectively. Corresponding results for tru-cut were 84.7%, 88.5% and 92.1%. In spite of differences reaching up to 9% in smaller nodules, intra-group results were not significant. CONCLUSION: Both needles have similar complications rate. Despite not having observed statistically significant differences between the two types of needles, end-cut devices have demonstrated a higher diagnostic yield in the three groups of nodules and could be a more suitable option especially for CNB of nodules ≤10 mm.