A Phase II Study of Telisotuzumab Vedotin in Patients With c–MET-positive Stage IV or Recurrent Squamous Cell Lung Cancer (LUNG-MAP Sub-study S1400K,NCT03574753)

IntroductionLung-MAP S1400K was designed to evaluate the response to telisotuzumab vedotin, an antibody-drug conjugate targeting c-MET, in patients with c-MET–positive squamous cell carcinoma (SCC).Patients and MethodsPatients with previously treated SCC with c-MET–positive tumors (H score ≥ 150, Ventana SP44 assay) were enrolled into 2 cohorts: Cohort 1 (immune checkpoint inhibitor-naive) and Cohort 2 (immune checkpoint inhibitor refractory). Telisotuzumab vedotin 2.7 mg/kg was administered intravenously every 3 weeks until disease progression or unacceptable toxicity. Response assessments were performed every 6 weeks. The primary endpoint was response by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints included progression-free survival, overall survival, response within cohort, duration of response, and toxicities. Interim analysis was planned after 20 evaluable patients, with ≥ 3 responses needed to continue enrollment.ResultsForty-nine patients (14% of screened patients) were assigned to S1400K, 28 patients enrolled (15 in Cohort 1 and 13 in Cohort 2), and 23 were eligible. S1400K closed on December 21, 2018 owing to lack of efficacy. Two responses (response rate of 9%; 95% confidence interval, 0%-20%) were reported in cohort 1 (1 complete and 1 unconfirmed partial response), whereas 10 patients had stable disease, with a disease control rate of 52%. The median overall and progression-free survival was 5.6 and 2.4 months, respectively. There were 3 grade 5 events (2 pneumonitis, in Cohort 2, and 1 bronchopulmonary hemorrhage, in Cohort 1).ConclusionTelisotuzumab vedotin failed to meet the pre-specified response needed to justify continuing enrollment to S1400K. Pneumonitis was an unanticipated toxicity observed in patients with SCC.     

Immune suppression in gliomas

Journal of Neuro-Oncology - The overall survival in patients with gliomas has not significantly increased in the modern era, despite advances such as immunotherapy. This is in part due to their...     

Chest computed tomography in children undergoing extra-corporeal membrane oxygenation: a 9-year single-centre experience

We retrospectively reviewed the imaging findings, indications, technique and clinical impact in children who had undergone chest CT while undergoing extra-corporeal membrane oxygenation (ECMO). Radiology and ECMO databases were searched to identify all 19 children who had undergone chest CT (20 scans in total) while on ECMO at our institution between May 2003 and May 2012. We reviewed all CT scans for imaging findings. Chest CT is performed in a minority of children on ECMO (4.5% in our series). Timing of chest CT following commencement of ECMO varied among patient groups but generally it was performed earlier in the neonatal group. Clinically significant imaging findings were found in the majority of chest CT scans. Many scans contained several findings, with most cases demonstrating parenchymal or pleural abnormalities. Case examples illustrate the spectrum of imaging findings, including underlying pathology such as necrotising pneumonia and severe barotrauma, and ECMO-related complications such as tension haemothoraces and cannula migration. The results of chest CT led to a change in patient management in 16 of 19 children (84%). There were no adverse events related to patient transfer. An understanding of scan technique and awareness of potential findings is important for the radiologist to provide prompt and optimal image acquisition and interpretation in appropriate patients.     

Maternal sounds elicit lower heart rate in preterm newborns in the first month of life

Background

The preferential response to mother's voice in the fetus and term newborn is well documented. However, the response of preterm neonates is not well understood and more difficult to interpret due to the intensive clinical care and range of medical complications.

Aim

This study examined the physiological response to maternal sounds and its sustainability in the first month of life in infants born very pretermaturely.

Methods

Heart rate changes were monitored in 20 hospitalized preterm infants born between 25 and 32 weeks of gestation during 30-minute exposure vs. non-exposure periods of recorded maternal sounds played inside the incubator. A total of 13,680 min of HR data was sampled throughout the first month of life during gavage feeds with and without exposure to maternal sounds.

Results

During exposure periods, infants had significantly lower heart rate compared to matched periods of care without exposure on the same day (p < .0001). This effect was observed in all infants, across the first month of life, irrespective of day of life, gestational age at birth, birth weight, age at testing, Apgar score, caffeine therapy, and requirement for respiratory support. No adverse effects were observed.

Conclusion

Preterm newborns responded to maternal sounds with decreased heart rate throughout the first month of life. It is possible that maternal sounds improve autonomic stability and provide a more relaxing environment for this population of newborns. Further studies are needed to determine the therapeutic implications of maternal sound exposure for optimizing care practices and developmental outcomes.