The following is a summary of “Young adults (YA) with non-small cell lung cancer (NSCLC): Snapshot of the oncogenic drivers and immune landscapes,” published in 2024 ASCO Annual Meeting under issue of Oncology by Pruitt et al.
A study using a large real-world dataset investigated the oncogenic drivers and immune landscape of non-small cell lung cancer (NSCLC) in younger adults (YA) (median age 71), a group representing only 5% of NSCLC cases.
Researchers conducted a retrospective study analyzing the underlying genetic mutations (oncogenic drivers) and immune system activity (immune landscapes) in younger adults with NSCLC, a subgroup representing only 5% of all NSCLC cases.
They analyzed 42,326 specimens with NSCLC at Caris Life Sciences, Phoenix, AZ, YA (<=50 years) were grouped into 18-30 (A1, n=61), 31-40 (A2, n=277), 41-50 (A3, n=1,549), and >50 years (A4, n=40,439). The TME composition was estimated using QuanTIseq from bulk RNA sequencing. The RW survival on Osimertinib (Osi-OS) was compared between ages 18-50 and >50 years, and HR was calculated via the Cox model. Significance was assessed using various tests and corrected for multiple comparisons (q<0.05).
The results showed YA with NSCLC had higher prevalence in females, non-smokers, and adenocarcinoma histology, ALK(IHC+), ROS1, RET, and NTRK1 fusion were enriched driver alterations in YA, while KRAS mutations were reduced. Interestingly, KRASG12D from transition and EGFRE746_A750 decreased with age, but KRASG12C from transversion increased in YA. The YA had improved Osi-OS (HR: 0.79, median Osi-OS=37.4 months vs 32 months in >50 years old, P=0.019). High tumor mutation burden (>=10 mut/Mb), mutations in TP53, KMT2D, NF1, RBM10, NFE2L2, and NOTCH1 increased with age, while GNAS decreased. Expression of immune checkpoint genes like PDCD1LG2 (A1/A4: 0.63, A3/A4: 0.89), LAG3 (A2/A4: 0.73, A3/A4: 0.89), and IFNG (A1/A4: 0.32, A3/A4: 0.75) decreased, while M2 macrophage (A2/A4: 1.2) and neutrophil (A2/A4: 1.2) increased in YA (all q<0.05).
Investigators found that YA with NSCLC displayed increased RET and NTRK1 gene fusions, different distributions of KRAS and EGFR mutations, and decreased immune gene expression compared to older adults.
Source: meetings.asco.org/abstracts-presentations/232143
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