The efficacy and potential limitations of molecular residual disease (MRD) detection urgently need to be fully elucidated in a larger population of non–small cell lung cancer (NSCLC). We enrolled 261 patients with stages I to III NSCLC who underwent definitive surgery, and 913 peripheral blood samples were successfully detected by MRD assay. Within the population, only six patients (3.2%) with longitudinal undetectable MRD recurred, resulting in a negative predictive value of 96.8%. Longitudinal undetectable MRD may define the patients who were cured. The peak risk of developing detectable MRD was approximately 18 months after landmark detection. Correspondingly, the positive predictive value of longitudinal detectable MRD was 89.1%, with a median lead time of 3.4 months. However, brain-only recurrence was less commonly detected by MRD (n = 1/5, 20%). Further subgroup analyses revealed that patients with undetectable MRD might not benefit from adjuvant therapy. Together, these results expound the value of MRD in NSCLC.
Significance:
This study confirms the prognostic value of MRD detection in patients with NSCLC after definitive surgery, especially in those with longitudinal undetectable MRD, which might represent the potentially cured population regardless of stage and adjuvant therapy. Moreover, the risk of developing detectable MRD decreased stepwise after 18 months since landmark detection.
Highlights
Our deep neural network based model represents the first finding of making use of H&E images to predict immunotherapy response.
Area under the curve (AUC) of 0.778(95% confidence interval, 0.638–0.905) was obtained on 54 melanoma H&E samples.
Our model was also validated on a second set of 55 lung cancer samples, yielding an AUC of 0.645 (95% confidence interval, 0.494–0.784), confirming the robustness of this model.
Herein, we characterize the landscape and prognostic significance of the T cell receptor (TCR) repertoire of early-stage non–small cell lung cancer (NSCLC) for patients with an epidermal growth factor receptor (
EGFR
) mutation. β Chain TCR sequencing was used to characterize the TCR repertoires of paraffin-preserved pretreatment tumor and tumor-adjacent tissues from 57 and 44 patients with stage II/III NSCLC with an
EGFR
mutation treated with gefitinib or chemotherapy in the ADJUVANT-CTONG 1104 trial. The TCR diversity was significantly decreased in patients with an
EGFR
mutation, and patients with high TCR diversity had a favorable overall survival (OS). A total of 10 TCR Vβ-Jβ rearrangements were significantly associated with OS. Patients with a higher frequency of Vβ5-6Jβ2-1, Vβ20-1Jβ2-1, Vβ24-1Jβ2-1, and Vβ29-1Jβ2-7 had significantly longer OS. Weighted combinations of the 4 TCRs were significantly associated with OS and disease-free survival (DFS) of patients, which could further stratify the high and low TCR diversity groups. Importantly, Vβ5-6Jβ2-1, Vβ20-1Jβ2-1, and Vβ24-1Jβ2-1 had a significant relationship with gefitinib treatment, while Vβ29-1Jβ2-7 was associated with chemotherapy. Four TCR Vβ-Jβ rearrangements related to favorable OS and DFS for adjuvant gefitinib and chemotherapy in patients with an
EGFR
mutation with stage II/III NSCLC; this may provide a novel perspective for the adjuvant setting for resectable NSCLC.
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