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<p><i>EGFR</i> status assessment is mandatory for adjuvant decision-making of resected stage IB-IIIA non-squamous non-small cell lung cancer (NS-NSCLC). It is questionable whether single-gene RT-PCR v<i>ersu</i>s next-generation sequencing (NGS) should be used for this evaluation. Moreover, co-occurring mutations have an impact on tumor behavior and may influence future therapeutic decision-making. We aimed to describe the clinico-pathological and molecular features, as well as the prognostic factors of resected <i>EGFR</i>-mutant NS-NSCLC evaluated with reflex NGS and RT-PCR, so as to compare the results of the two methods. We retrospectively included and collected data from patients with resected <i>EGFR-</i>mutant NS-NSCLC diagnosed in our institution between 2005 and 2024. Additional cases from another center were included. Tumors were analyzed using targeted NGS and RT-PCR. A total of 153 patients were selected. The median follow-up after surgery was 22&#xa0;months. The positive percent agreement of RT-PCR compared to NGS for the detection of an <i>EGFR</i> mutation was 88%. Common single <i>EGFR</i> mutations (L858R/del19) were observed in 117/153 (77%) cases; 22/153 (14%) and 14/153 (9%) cases had uncommon single and compound <i>EGFR</i> mutations, respectively. 63/153 (41%) patients had a co-occurring mutation, including a <i>TP53</i> mutation in 43/63 (68%) co-mutated patients. <i>EGFR/TP53</i>-mutant tumors were associated with positive PD-L1 expression compared to <i>EGFR</i>-mutant/<i>TP53</i>-wild-type tumors (62% vs 39%; <i>p</i> = 0.006). Shorter median event-free survival (EFS) in patients with an <i>EGFR</i> exon 18 mutation and those with <i>TP53</i> exon 7 co-mutation was recorded. The <i>EGFR</i> status should be systematically evaluated using targeted NGS reflex testing for resected NS-NSCLC since future therapeutic decision-making could soon consider integrating the presence of co-occurring mutations<i>.</i></p>

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EGFR status assessment using reflex testing targeted next-generation sequencing for resected non-squamous non-small cell lung cancer

  • 期刊论文

  • 发表日期：

    2024年12月31日

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  • Samantha Goffinet,
  • Christophe Bontoux,
  • Simon Heeke,
  • Federica Pezzuto,
  • Marius Ilié,
  • Elodie Long-Mira,
  • Sandra Lassalle,
  • Olivier Bordone,
  • Virginie Lespinet,
  • Maryline Allégra,
  • Virginie Tanga,
  • Christelle Bonnetaud,
  • Georges Garnier,
  • Jonathan Benzaquen,
  • Charlotte Cohen,
  • Victoria Ferrari,
  • Charles Marquette,
  • Jean Philippe Berthet,
  • Fiorella Calabrese,
  • Paul Hofman,
  • Véronique Hofman

摘要

EGFR status assessment is mandatory for adjuvant decision-making of resected stage IB-IIIA non-squamous non-small cell lung cancer (NS-NSCLC). It is questionable whether single-gene RT-PCR versus next-generation sequencing (NGS) should be used for this evaluation. Moreover, co-occurring mutations have an impact on tumor behavior and may influence future therapeutic decision-making. We aimed to describe the clinico-pathological and molecular features, as well as the prognostic factors of resected EGFR-mutant NS-NSCLC evaluated with reflex NGS and RT-PCR, so as to compare the results of the two methods. We retrospectively included and collected data from patients with resected EGFR-mutant NS-NSCLC diagnosed in our institution between 2005 and 2024. Additional cases from another center were included. Tumors were analyzed using targeted NGS and RT-PCR. A total of 153 patients were selected. The median follow-up after surgery was 22 months. The positive percent agreement of RT-PCR compared to NGS for the detection of an EGFR mutation was 88%. Common single EGFR mutations (L858R/del19) were observed in 117/153 (77%) cases; 22/153 (14%) and 14/153 (9%) cases had uncommon single and compound EGFR mutations, respectively. 63/153 (41%) patients had a co-occurring mutation, including a TP53 mutation in 43/63 (68%) co-mutated patients. EGFR/TP53-mutant tumors were associated with positive PD-L1 expression compared to EGFR-mutant/TP53-wild-type tumors (62% vs 39%; p = 0.006). Shorter median event-free survival (EFS) in patients with an EGFR exon 18 mutation and those with TP53 exon 7 co-mutation was recorded. The EGFR status should be systematically evaluated using targeted NGS reflex testing for resected NS-NSCLC since future therapeutic decision-making could soon consider integrating the presence of co-occurring mutations.