Simon Trotter

BACKGROUND: Among patients with non-small-cell lung cancer (NSCLC), data on intratumor heterogeneity and cancer genome evolution have been limited to small retrospective cohorts. We wanted to prospectively investigate intratumor heterogeneity in relation to clinical outcome and to determine the clonal nature of driver events and evolutionary processes in early-stage NSCLC. METHODS: In this prospective cohort study, we performed multiregion whole-exome sequencing on 100 early-stage NSCLC tumors that had been resected before systemic therapy. We sequenced and analyzed 327 tumor regions to define evolutionary histories, obtain a census of clonal and subclonal events, and assess the relationship between intratumor heterogeneity and recurrence-free survival. RESULTS: ), which remained significant in multivariate analysis. CONCLUSIONS: Intratumor heterogeneity mediated through chromosome instability was associated with an increased risk of recurrence or death, a finding that supports the potential value of chromosome instability as a prognostic predictor. (Funded by Cancer Research UK and others; TRACERx ClinicalTrials.gov number, NCT01888601 .).

to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches.

A young female vaper presented with insidious onset cough, progressive dyspnoea on exertion, fever, night sweats and was in respiratory failure when admitted to hospital. Clinical examination was unremarkable. Haematological tests revealed only thrombocytopenia, which was long standing, and her biochemical and inflammatory markers were normal. Chest radiograph and high-resolution CT showed diffuse ground-glass infiltrates with reticulation. She was initially treated with empirical steroids and there was improvement in her oxygenation, which facilitated further tests. Since the bronchoscopy and high-volume lavage was unyielding, a video-assisted thoracoscopicsurgical biopsy was done later and was suggestive of lipoid pneumonia. The only source of lipid was the vegetable glycerine found in e-cigarette (EC). Despite our advice to quit vaping, she continued to use EC with different flavours and there is not much improvement in her clinical and spirometric parameters.

A fetus with intrapericardial teratoma had a large pericardial effusion diagnosed by echocardiography. Cardiac tamponade, a common cause of fetal death, was averted by intrauterine pericardiocentesis. Planned obstetric and neonatal management permitted surgical treatment before cardiorespiratory distress developed. The tumor was completely excised and the infant is asymptomatic.