Search

We report a personalized tumor-informed technology, Patient-specific pROgnostic and Potential tHErapeutic marker Tracking (PROPHET) using deep sequencing of 50 patient-specific variants to detect molecular residual disease (MRD) with a limit of detection of 0.004%. PROPHET and state-of-the-art fixed-panel assays were applied to 760 plasma samples from 181 prospectively enrolled early stage non-small cell lung cancer patients. PROPHET shows higher sensitivity of 45% at baseline with circulating tumor DNA (ctDNA). It outperforms fixed-panel assays in prognostic analysis and demonstrates a median lead-time of 299 days to radiologically confirmed recurrence. Personalized non-canonical variants account for 98.2% with prognostic effects similar to canonical variants. The proposed tumor-node-metastasis-blood (TNMB) classification surpasses TNM staging for prognostic prediction at the decision point of adjuvant treatment. PROPHET shows potential to evaluate the effect of adjuvant therapy and serve as an arbiter of the equivocal radiological diagnosis. These findings highlight the potential advantages of personalized cancer techniques in MRD detection. [Display omitted] • PROPHET outperforms fixed-panel MRD assays in head-to-head comparison in NSCLC • TNMB stage, integrating landmark ctDNA MRD and TNM, improves prognosis prediction • PROPHET illustrates a median lead time of 299 days to radiological recurrence • Post-relapse ctDNA status facilitates decision on later lines of treatment Chen et al. introduce personalized Patient-specific pROgnostic and Potential tHErapeutic marker Tracking (PROPHET) for detecting molecular residual disease (MRD) in NSCLC, featuring a notably low limit of detection (LOD). It exhibits elevated sensitivity and extended lead time than radiologically confirmed recurrence. It also facilitates prognostic accuracy and postoperative treatment evaluation. [ABSTRACT FROM AUTHOR]

Introduction Anaplastic lymphoma kinase ( ALK ) rearrangements are present in approximately 5% of non-small-cell lung cancers (NSCLCs). NSCLCs with ALK -rearrangement can be effectively treated with crizotinib. However, magnitude and duration of responses are found to be heterogeneous. This study explored the clinical efficacy of crizotinib in different ALK variants. Methods Among 96 ALK -rearrangement patients treated with crizotinib, 60 patients were identified with tumor specimens that could be evaluated by next-generation sequencing (NGS). We retrospectively evaluated the efficacy of crizotinib in different ALK variants. Results The median Progression-free survival (PFS) of the 96 ALK -rearrangement patients was 14.17 months. Among the 60 patients with NGS results, the most frequent variants were variant 3a/b (33.33%), variant 1 (23.33%) and variant 2 (15.00%). The percentage of rare EML4 - ALK variants and non EML4 - ALK variants were 10.00% and 18.33%. Survival analysis showed that patients with variant 2 appeared to have longer PFS than others (P = .021); also, patients with TP53 mutation seemed to have an unfavorable PFS than those with TP53 wild-type with a borderline p value (P = .068). After adjusting for other baseline characteristics, EML4 - ALK variant 2 was identified as an important factor for a better PFS of crizotinib. We also found that patients with variant 3a/b had shorter duration of response to crizotinib; however, no significant difference of PFS was observed between the PFS of variant3a/b and non-v3 EML4 - ALK variants. Conclusions Our results indicate prolonged PFS in patients with EML4 - ALK variant 2. [ABSTRACT FROM AUTHOR]