Prediction of recurrence in stage I EGFR mutation-positive NSCLC: Combination of CT appearance and selected co-occurring gene alterations by machine learning.

Authors

Akiko Tateishi

Akiko Tateishi

Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan

Akiko Tateishi , Hidehito Horinouchi , Ken Takasawa , Nobuji Kouno , Takaaki Mizuno , Yu Okubo , Yukihiro Yoshida , Shun-ichi Watanabe , Mototaka Miyake , Masahiko Kusumoto , Koji Inaba , Hiroshi Igaki , Yasushi Yatabe , Masami Mukai , Katsuya Tanaka , Naoki Mihara , Kouya Shiraishi , Takashi Kohno , Yuichiro Ohe , Ryuji Hamamoto

Organizations

Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan, Division of Medical AI Research and Development, National Cancer Center Research Institute, Tokyo, Japan, Department of Thoracic Oncology , National Cancer Center Hospital, Tokyo, Japan, Department of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan, Department of Diagnostic Radiology, National Cancer Center Hospital, Tokyo, Japan, National Cancer Center Hospital, Tokyo, Japan, Tokyo, Japan, Department of Radiation Oncology, National Cancer Center Hospital, Japan, Tokyo, Japan, Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan, Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan, Division of Medical Informatics, National Cancer Center Hospital, Tokyo, Japan, Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan, National Cancer Center Hospital, Tokyo, Japan

Research Funding

No funding sources reported

Background: Predicting the risk of postoperative recurrence is becoming increasingly important in patients (pts) with resectable EGFR mutation positive (EGFRm) non-small cell lung cancer (NSCLC) after the ADAURA trial. The presence of non-solid ground-grass opacity (GGO) component on computed tomography (CT) images is known to affect the prognosis of stage I lung cancer. Only a few reports investigating the relationship between gene alterations and CT images in stage I EGFRm NSCLC. Methods: We have developed a machine learning-based model to predict recurrence within five years in TNM stage I (UICC 8th) EGFRm NSCLC pts who underwent surgery between 1985 and 2019 using whole exome sequencing in the PRISM project. We evaluated the pts’ characteristics, recurrence-free survival (RFS), the CT appearance (pure GGO and part solid [GGO]), without GGO [pure solid]), and consolidation tumor ratio (CTraio). Then, we analyzed the correlation between the image findings and gene alterations predicting a high risk of recurrence. Results: Among 1351 pts, stage I, EGFRm were 308 (22.8%). The median RFS for stage I EGFR-m pts was 123.2 months (m). In the prediction model, TP53 and RBM10 genes were among the gene alterations that had a high impact on the high-risk recurrence within five years. Among the 302 stage I, EGFRm pts for whom CT images were available, 166 (55.6%) pts had GGO, and 137 (45.4%) pts had pure solid appearance. The median CTratio was 0.87. The median RFS was not reached (NR) for GGO, 86.5m for pure solid (hazard ratio [HR] 2.42 [1.58-3.73], p<0.0001). There was a negative correlation indicating that the larger the CTratio, the shorter the RFS (p<0.0047). The proportion of TP53 mutation (TP53m) was lower in GGO and higher in pure solid (p<0.0001, Table). The median RFS was NR for GGO plus TP53m-negative pts, was 119.7m for GGO plus TP53m-positive pts, 84.8m for pure solid plus TP53m-negative pts, and 98.8m for pure solid plus TP53m-positive pts, respectively. Among pts with 0≦CTratio<0.5 46 (15.2%), with 0.5≦CTratio<1 119 (39.4%), and with CTratio=1 137 (45.4%), the proportion of TP53m increased as the CTratio increased. Conclusions: We found a linear relationship between CTratio and proportion of co-occurring TP53m with EGFRm. Combination of CT appearance (GGO or pure solid) and co-occurring TP53m can predict recurrence in stage I, EGFRm NSCLC.

GGOPure Solid (without GGO)
n (%)165 (54.6)137 (45.4)
median RFS (m), 95%CINR (119.7-NR)86.5 (71.0-107.4)
5year RFS rate (%)82.964.2
HR (95%CI), p-value12.42 (1.58-3.73), p<0.0001
Co-occurring TP53-mutationnegativepositivenegativepositive
n (%)135 (81.8)30 (18.2)81 (59.1)56 (40.9)
median RFS (m), 95%CINR (123.2-NR)119.7 (53.1-NR)84.8 (70.8-NR)98.8 (57.1-NR)
5year RFS rate (%)83.858.761.160.0
HR (95%CI)12.24 (1.07-4.70)2.87 (1.68-4.91)2.94 (1.65-5.21)

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Abstract Details

Meeting

2024 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers

Track

Lung Cancer

Sub Track

Local-Regional Non–Small Cell Lung Cancer

Citation

J Clin Oncol 42, 2024 (suppl 16; abstr 8053)

DOI

10.1200/JCO.2024.42.16_suppl.8053

Abstract #

8053

Poster Bd #

315

Abstract Disclosures

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