Assessment of RANK/RANK-L prevalence and clinical significance in NSCLC European Thoracic Oncology Platform Lungscape cohort and SPLENDOUR randomized clinical trial
Background - The primary objective of this study is to evaluate the clinical significance of RANK/L expression, in both a retrospective cohort of surgically resected stage I-III NSCLC (Lungscape) and a randomized clinical trial-cohort (SPLENDOUR) of advanced NSCLC treated with chemotherapy alone or...
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| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
January 2023
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| In: |
Lung cancer
Year: 2023, Volume: 175, Pages: 141-151 |
| ISSN: | 1872-8332 |
| DOI: | 10.1016/j.lungcan.2022.12.004 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.lungcan.2022.12.004 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0169500222007139 
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| Author Notes: | Solange Peters, Igor Letovanec, Murielle Mauer, Urania Dafni, Dunson Ejedepang, Wojciech Biernat, Lukas Bubendorf, Arne Warth, Saraswati Pokharel, Niels Reinmuth, Margarita Majem Tarruella, Jose Casas-Martin, Zoi Tsourti, Nesa Marti, Roswitha Kammler, Sarah Danson, Mary O'Brien, Rolf. A. Stahel |
| Summary: | Background - The primary objective of this study is to evaluate the clinical significance of RANK/L expression, in both a retrospective cohort of surgically resected stage I-III NSCLC (Lungscape) and a randomized clinical trial-cohort (SPLENDOUR) of advanced NSCLC treated with chemotherapy alone or in combination with denosumab. - Methods - RANK-L expression was assessed on tissue microarrays (TMAs) in Lungscape and whole sections in SPLENDOUR, using immunohistochemistry, with H-scores values > 0 indicating positivity. Prevalence of RANK positivity and its association with clinicopathological characteristics, and patient outcome was explored in a subset of the ETOP Lungscape cohort and in SPLENDOUR. Also investigated were the prevalence of RANK overexpression (proportion of positive cancer cells ≥ 50%) in the Lungscape cohort, and RANK-L in the SPLENDOUR trial. - Results - In the Lungscape cohort, RANK expression was assessed at a median follow-up of 46 months (N = 488 patients; 4 centers); 35% were female, 44/49/6% adenocarcinomas (AC)/squamous cell carcinomas (SCC)/other, 48/27/25% with stage I/II/III. Median RFS/TTR/OS were 58/Not reached/74 months. Prevalence of RANK expression was 31% (95%CI:27%-35%); significantly higher in AC: 50% (95%CI:43%-57%) vs SCC: 12% (95%CI:8%-16%) (p < 0.001); more frequent in females (42% vs 25%, p < 0.001) and tumors ≤ 4 cm (35.3% vs 23.3%, p = 0.0065). No association with outcome was found. In the SPLENDOUR trial (463 patients), the prevalence of membranous and cytoplasmic RANK positivity was 34% (95%CI:30%-38%) and 9% (95%CI:7%-12%), respectively, while prevalence for RANK-L was 5% (95%CI:3%-7%) and 36% (95%CI:31%-40%), respectively. Cytoplasmic RANK-L positivity was more common among females (47% vs 31%, p = 0.001) and in non-SCC histology (45% vs 10%, p < 0.0001). At the pre-specified 1% significance level, no prognostic or predictive effect was found. - Conclusions - Both cohorts indicate that RANK expression is more common in adenocarcinoma/non-squamous NSCLC and in female patients. No prognostic effect is found, and in the clinical trial involving addition of denosumab to chemotherapy no predictive effect is detected. |
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| Item Description: | Published: 13 December 2022 Gesehen am 27.06.2023 |
| Physical Description: | Online Resource |
| ISSN: | 1872-8332 |
| DOI: | 10.1016/j.lungcan.2022.12.004 |