Abstract
PurposeCheckpoint inhibition therapy using monoclonal antibodies against programmed cell death protein 1 (PD-1) or its ligand (PD-L1) is now standard management of non-small cell lung cancer (NSCLC). PD-L1 expression is a validated and approved prognostic and predictive biomarker for anti-PD-1/PD-L1 therapy. Technetium-99 m [99mTc]-labelled anti-PD-L1 single-domain antibody (NM-01) SPECT/CT quantification correlates with PD-L1 expression in NSCLC, presenting an opportunity for non-invasive assessment. The aim of this study was to determine the inter- and intraobserver agreement of the quantitative assessment of [99mTc]NM-01 SPECT/CT in NSCLC.Methods[99mTc]NM-01 SPECT/CT studies of 21 consecutive NSCLC participants imaged for the evaluation of PD-L1 expression were analysed. Three independent observers measured maximum counts in a tumour region of interest (ROImax) of primary lung, metastatic lesions and normal tissue references of both 1 and 2 h post-injection (n = 42) anonymised studies using a manual technique. Intraclass correlation coefficients (ICC) were calculated, and Bland–Altman plot analysis was performed to determine inter- and intraobserver agreement.ResultsIntraclass correlation of primary lung tumour-to-blood pool (T:BP; ICC 0.83, 95% CI 0.73–0.90) and lymph node metastasis-to-blood pool (LN:BP; ICC 0.87, 0.81–0.92) measures of [99mTc]NM-01 uptake was good to excellent between observers. Freehand ROImax of T (ICC 0.94), LN (ICC 0.97), liver (ICC 0.97) and BP (ICC 0.90) reference tissues also demonstrated excellent interobserver agreement. ROImax scoring of healthy lung demonstrated moderate to excellent interobserver agreement (ICC 0.84) and improved when measured consistently at the level of the aortic arch (ICC 0.89). Manual ROImax re-scoring of T, LN, T:BP and LN:BP using [99mTc]NM-01 SPECT/CT following a 42-day interval was consistent with excellent intraobserver agreement (ICC range 0.95–0.97).ConclusionGood to excellent inter- and intraobserver agreement of the quantitative assessment of [99mTc]NM-01 SPECT/CT in NSCLC was demonstrated in this study, including T:BP which has been shown to correlate with PD-L1 status. [99mTc]NM-01 SPECT/CT has the potential to reliably and non-invasively assess PD-L1 expression.Clinical trial registrationClinicalTrials.gov identifier no. NCT02978196. Registered 30th November 2016.
Highlights
A [99mTc]-labelled anti-PD-L1 single-domain antibody (NM-01) SPECT/CT quantification correlates with PD-L1 expression in non-small cell lung cancer (NSCLC), presenting an opportunity for non-invasive assessment
T Results: Intraclass correlation of primary lung tumour-to-blood pool (T:Blood pool (BP); Intraclass correlation coefficients (ICC) 0.83, 95% confidence interval (CI) 0.73–0.90) and lymph node metastasis-to-blood pool (LN:BP; ICC 0.87, 0.81–0.92) measures of [99mTc]NM-01 uptake was good to excellent
A erative Oncology Group (ECOG) performance score of PD-L1 expression determined by immunohistochemistry (IHC) is a widely validated biomarker correlating with anti-PD-1/PD-L1 therapeutic response and sur
Summary
A [99mTc]-labelled anti-PD-L1 single-domain antibody (NM-01) SPECT/CT quantification correlates with PD-L1 expression in NSCLC, presenting an opportunity for non-invasive assessment. The aim of this study was to determine the interand intraobserver agreement of the quantitative assessment of [99mTc]NM-01 SPECT/CT in NSCLC. Three independent observers measured maximum counts in a tumour region of interest. (ROImax) of primary lung, metastatic lesions and normal tissue references of both 1 and 2 h post-injection (n = 42). Intraclass correlation coefficients (ICC) were calculated, and Bland–Altman plot analysis was performed to determine inter- and intraobserver agreement. Freehand ROImax of T (ICC 0.94), LN (ICC 0.97), liver (ICC 0.97) and BP (ICC 0.90) reference tissues demonstrated excellent interobserver agreement. ROImax scoring of healthy lung demonstrated moderate to excellent interobserver agreement (ICC 0.84) and improved when measured consistently at the level of the aortic arch Freehand ROImax of T (ICC 0.94), LN (ICC 0.97), liver (ICC 0.97) and BP (ICC 0.90) reference tissues demonstrated excellent interobserver agreement. ROImax scoring of healthy lung demonstrated moderate to excellent interobserver agreement (ICC 0.84) and improved when measured consistently at the level of the aortic arch
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