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Objectives <p>Subsolid nodules emerged as frequent radiological variants of lung adenocarcinoma. Radiological features including solid-component prevalence and larger tumour dimensions prompt tumoral invasiveness guiding prognosis and management. Thus, we aimed to clarify the molecular grounds that dictate these radiological appearances and clinical behaviour in a real-life European-cohort. Additionally, following the growing interest toward targeted-therapies in early-stage diseases, we aimed to present real-life epidemiological data of actionable mutations in these patients.</p> Methods <p>In this retrospective single-centre study, targeted next-generation sequencing was performed continuatively in all the resected subsolid lung adenocarcinomas in the period between May 2016 and December 2023. Clinico-radiological data were collected. The genetic landscape of our real-life European subsolid adenocarcinoma population is defined. Common and actionable mutations (frequency &gt; 5%) relation to key clinico-radiological features are evaluated.</p> Results <p>Overall, 156 subsolid adenocarcinomas were analysed. <i>KRAS</i>-mutations, mostly <i>KRAS p.G12C</i>, were the most prevalent followed by <i>EGFR</i>, including 25% uncommon <i>EGFR</i>-mutations, <i>TP53</i> and <i>MET</i> mutations. Amongst the clinico-radiological variables, <i>KRAS</i>-mutations and <i>KRAS p.G12C</i>-mutation were associated to smoking history (≥ 20 pack/years), aggressive histologic subtype and higher consolidation-to-tumor ratio (CTR). Moreover, <i>KRAS</i>-mutated nodules had faster tumour-doubling-time. Conversely, <i>EGFR</i>-mutations were associated to female sex and lower CTR. The latter not being confirmed in common <i>EGFR</i>-mutations. Additionally, in common <i>EGFR</i>-mutated nodules, aggressive histological components were rarer.</p> Conclusion <p>Our study presents the molecular profile of subsolid lung adenocarcinoma in a real-life European-cohort. <i>KRAS</i>-mutations were the most prevalent, and were related to smoking history, higher CTR and faster growth. Conversely, common <i>EGFR</i>-mutations were rarer than expected and unrelated to smoking history and radiological features.</p>

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Molecular characterization of early-stage lung adenocarcinoma presenting as subsolid nodules in a real-life European cohort

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月9日

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  • Riccardo Tajè,
  • Filippo Tommaso Gallina,
  • Mauro Caterino,
  • Daniele Forcella,
  • Alexandro Patirelis,
  • Gabriele Alessandrini,
  • Simonetta Buglioni,
  • Fabiana Letizia Cecere,
  • Francesca Fusco,
  • Federico Cappelli,
  • Enrico Melis,
  • Paolo Visca,
  • Federico Cappuzzo,
  • Vincenzo Ambrogi,
  • Antonello Vidiri

摘要

Objectives

Subsolid nodules emerged as frequent radiological variants of lung adenocarcinoma. Radiological features including solid-component prevalence and larger tumour dimensions prompt tumoral invasiveness guiding prognosis and management. Thus, we aimed to clarify the molecular grounds that dictate these radiological appearances and clinical behaviour in a real-life European-cohort. Additionally, following the growing interest toward targeted-therapies in early-stage diseases, we aimed to present real-life epidemiological data of actionable mutations in these patients.

Methods

In this retrospective single-centre study, targeted next-generation sequencing was performed continuatively in all the resected subsolid lung adenocarcinomas in the period between May 2016 and December 2023. Clinico-radiological data were collected. The genetic landscape of our real-life European subsolid adenocarcinoma population is defined. Common and actionable mutations (frequency > 5%) relation to key clinico-radiological features are evaluated.

Results

Overall, 156 subsolid adenocarcinomas were analysed. KRAS-mutations, mostly KRAS p.G12C, were the most prevalent followed by EGFR, including 25% uncommon EGFR-mutations, TP53 and MET mutations. Amongst the clinico-radiological variables, KRAS-mutations and KRAS p.G12C-mutation were associated to smoking history (≥ 20 pack/years), aggressive histologic subtype and higher consolidation-to-tumor ratio (CTR). Moreover, KRAS-mutated nodules had faster tumour-doubling-time. Conversely, EGFR-mutations were associated to female sex and lower CTR. The latter not being confirmed in common EGFR-mutations. Additionally, in common EGFR-mutated nodules, aggressive histological components were rarer.

Conclusion

Our study presents the molecular profile of subsolid lung adenocarcinoma in a real-life European-cohort. KRAS-mutations were the most prevalent, and were related to smoking history, higher CTR and faster growth. Conversely, common EGFR-mutations were rarer than expected and unrelated to smoking history and radiological features.