Assessment of RANK/RANK-L prevalence and clinical significance in NSCLC European Thoracic Oncology Platform Lungscape cohort and SPLENDOUR randomized clinical trial
Por:
Peters S., Letovanec I., Mauer M., Dafni U., Ejedepang D., Biernat W., Bubendorf L., Warth A., Pokharel S., Reinmuth N., Tarruella, MM, Casas-Martin J., Tsourti Z., Marti N., Kammler R., Danson S., O'Brien M., Stahel R.A.
Publicada:
1 ene 2023
Ahead of Print:
1 dic 2022
Resumen:
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.
Filiaciones:
Peters S.:
CHU Vaudois, Dept Oncol, Lausanne, Switzerland
Letovanec I.:
CHU Vaudois, Dept Pathol, Lausanne, Switzerland
Hop Valais, ICH, Sion, Switzerland
Mauer M.:
European Org Res & Treatment Canc EORTC, 83 Ave E Mounier, B-1200 Brussels, Belgium
Dafni U.:
Frontier Sci Fdn Hellas, Athens, Greece
Natl & Kapodistrian Univ Athens, Athens, Greece
Ejedepang D.:
European Org Res & Treatment Canc EORTC, 83 Ave E Mounier, B-1200 Brussels, Belgium
Biernat W.:
Med Univ Gdansk, Dept Pathomorphol, Gdansk, Poland
Bubendorf L.:
Univ Hosp Basel, Inst Med Genet & Pathol, Basel, Switzerland
Warth A.:
Univ Klinikum Heidelberg, Dept Pathol, Heidelberg, Germany
UEGP Giessen Wetzlar Limburg, Inst Pathol Cytopathol & Mol Pathol MVZ, Wetzlar, Germany
Pokharel S.:
Roswell Park Comprehens Canc Ctr, Dept Pathol, Buffalo, NY USA
Reinmuth N.:
Asklepios Fachkliniken Muenchen Gauting, Asklepios Kliniken GmbH, Dept Oncol, Munich, Germany
Tarruella, MM:
Hosp Santa Creu & Sant Pau, Dept Oncol, Barcelona, Spain
Casas-Martin J.:
European Org Res & Treatment Canc EORTC, 83 Ave E Mounier, B-1200 Brussels, Belgium
Tsourti Z.:
Frontier Sci Fdn Hellas, Athens, Greece
Marti N.:
ETOP IBCSG Partners Fdn, Translat Res Coordinat, Bern, Switzerland
Kammler R.:
ETOP IBCSG Partners Fdn, Translat Res Coordinat, Bern, Switzerland
Danson S.:
Univ Sheffield, Dept Oncol & Metab, Weston Pk Hosp, Sheffield, S Yorkshire, England
Univ Sheffield, Weston Pk Hosp, Sheffield Expt Canc Med Ctr, Sheffield, S Yorkshire, England
O'Brien M.:
Royal Marsden Hosp Sutton, Dept Med Oncol, Sutton, Surrey, England
Stahel R.A.:
ETOP IBCSG Partners Fdn, Coordinating Ctr, Bern, Switzerland
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