Radiotherapy is not currently informed by the genetic composition of an individual patient's tumour. To identify genetic features regulating survival after DNA damage, here we conduct large-scale profiling of cellular survival after exposure to radiation in a diverse collection of 533 genetically annotated human tumour cell lines. We show that sensitivity to radiation is characterized by significant variation across and within lineages. We combine results from our platform with genomic features to identify parameters that predict radiation sensitivity. We identify somatic copy number alterations, gene mutations and the basal expression of individual genes and gene sets that correlate with the radiation survival, revealing new insights into the genetic basis of tumour cellular response to DNA damage. These results demonstrate the diversity of tumour cellular response to ionizing radiation and establish multiple lines of evidence that new genetic features regulating cellular response after DNA damage can be identified.
on behalf of the AQuIRE Bronchoscopy Registry BACKGROUND: Th ere is signifi cant variation between physicians in terms of how they perform therapeutic bronchoscopy, but there are few data on whether these differences impact eff ectiveness.
and Michael Simoff , MD , FCCP ; on behalf of the AQuIRE Bronchoscopy Registry BACKGROUND: Th ere are signifi cant variations in how therapeutic bronchoscopy for malignant airway obstruction is performed. Relatively few studies have compared how these approaches aff ect the incidence of complications.
Idiopathic subglottic stenosis (iSGS) is a fibrotic disease of unclear etiology that produces obstruction of the central airway in the anatomic region under the glottis. The diagnosis of this entity is difficult, usually delayed and confounded with other common respiratory diseases. No apparent etiology is identified even after a comprehensive workup that includes a complete history, physical examination, pulmonary function testing, auto-antibodies, imaging studies, and endoscopic procedures. This approach, however, helps to exclude other conditions such as granulomatosis with polyangiitis (GPA). It is also helpful to characterize the lesion and outline management strategies. Therapeutic endoscopic procedures and surgery are the most common management modalities, but medical therapy can also play a significant role in preventing or delaying recurrence. In this review, we describe the morphology, pathophysiology, clinical presentation, evaluation, management, and prognosis of iSGS.
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