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Background: Body mass index (BMI) both before and after heart transplant (HT) is used to risk stratify in adult HT. Single-center studies identify BMI as a potential predictor of outcome after HT in children; large-scale analyses in pediatric HT have not been performed. Methods: The ISHLT pediatric heart transplant registry was queried for HT recipients >2 years old between 1996 and 2006 with data for BMI percentile (BMI%ile) at HT. Survival and morbidity rates post-HT were compared between BMI%ile cohorts defined as: wasted, <5th BMI%ile; normal, 5th to 95th BMI%ile; and obese, >95th BMI%ile at HT. Results: Data from 2,333 pediatric HT patients were available for analysis. Incidence of abnormal BMI%ile at HT was: wasted = 23% and obese = 8%. Wasting and obesity were similar in patients with congenital or cardiomyopathic diagnoses. Wasted or obese patients at HT did not differ from patients with normal BMI in survival on Kaplan–Meier or multivariate analyses. There were no significant differences in pre-, peri- or post-operative adverse events between patients with wasting or obesity and those with normal BMI%ile at HT. Conclusions: In contrast to adults, abnormal body mass at time of transplant was not associated with decreased survival in pediatric HT recipients. Potential pediatric transplant candidates should not be excluded based on the perception that wasting or obesity will increase the risk of adverse outcomes. [Copyright &y& Elsevier]

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]

Highlights • De novo T790 M is significantly more likely to coexist with EGFR L858R than with 19del in NSCLC. • The relative allele frequency of T790 M mutation may serve as a predictive biomarker for treatment response to EGFR-TKIs. • Osimertinib is potentially an effective drug for the treatment of advanced NSCLC with de novo T790 M. Abstract Introduction De novo T790 M mutation in EGFR has been reported in various studies. However, its genetic characteristics and association with EGFR tyrosine kinase inhibitors (TKIs) treatment response remain poorly studied. Methods We retrospectively screened 1228 consecutive non-small cell lung cancer (NSCLC) patients and identified 29 de novo T790 M carriers. Capture-based targeted deep sequencing was conducted on 21 eligible samples as well as a 20-sample cohort with acquired T790 M mutation after EGFR-TKIs treatment. We characterized and compared their mutational profiles using a panel consisting of 168 lung cancer-related genes. Results De novo T790 M mutation was found in 5.8% of the TKI-naive patients harboring EGFR activating mutations. Among the de novo T790 M samples, T790 M was significantly more likely to coexist with L858R than with 19del (76.2% vs. 23.8%) compared to the acquired T790 M cohort (30.0% vs. 70.0%) (p = 0.003). These two groups harbored different concurrent gene mutations as well. Notably, the ratio of allele frequency (AF) of the T790 M mutation to the EGFR activating mutation in each patient, defined as the T790 M relative AF (RAF), differed significantly between the de novo and acquired T790 M cohorts (86.1% vs. 22.3%, p < 0.0001). Among the 10 patients with de novo T790 M who received the 1st-generation EGFR-TKIs treatment, interestingly, the only one who achieved partial response (PR) had the lowest T790 M RAF of 19.7%. The other 9 patients with an average T790 M RAF of 85.9% (±22.6%) achieved stable disease or progressive disease as the best response. One patient, treated with osimertinib after erlotinib failure, achieved PR and the therapeutic response sustained for more than 14.5 months. Conclusion The molecular characteristics of de novo T790 M carriers differ distinctly from acquired T790 M carriers. The RAF of EGFR T790 M mutation may serve as a predictive biomarker for treatment response to EGFR-TKIs. Osimertinib is potentially an effective drug for the treatment of NSCLC with de novo T790 M. [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]