Background Although EGFR mutant tumors exhibit low response rates to immune checkpoint blockade overall, some EGFR mutant tumors do respond to these therapies; however, there is a lack of understanding of the characteristics of EGFR mutant lung tumors responsive to immune checkpoint blockade. Patients and methods We retrospectively analyzed de-identified clinical and molecular data on 171 cases of EGFR mutant lung tumors treated with immune checkpoint inhibitors from the Yale Cancer Center, Memorial Sloan Kettering Cancer Center, University of California Los Angeles, and Dana Farber Cancer Institute. A separate cohort of 383 EGFR mutant lung cancer cases with sequencing data available from the Yale Cancer Center, Memorial Sloan Kettering Cancer Center, and The Cancer Genome Atlas was compiled to assess the relationship between tumor mutation burden and specific EGFR alterations. Results Compared with 212 EGFR wild-type lung cancers, outcomes with programmed cell death 1 or programmed death-ligand 1 (PD-(L)1) blockade were worse in patients with lung tumors harboring alterations in exon 19 of EGFR ( EGFR Δ19 ) but similar for EGFR L858R lung tumors. EGFR T790M status and PD-L1 expression did not impact response or survival outcomes to immune checkpoint blockade. PD-L1 expression was similar across EGFR alleles. Lung tumors with EGFR Δ19 alterations harbored a lower tumor mutation burden compared with EGFR L858R lung tumors despite similar smoking history. Conclusions EGFR mutant tumors have generally low response to immune checkpoint inhibitors, but outcomes vary by allele. Understanding the heterogeneity of EGFR mutant tumors may be informative for establishing the benefits and uses of PD-(L)1 therapies for patients with this disease.

Background Diffuse parenchymal lung diseases (DPLDs) are common. An accurate diagnosis is essential due to differences in etiology, cli nicopathologic features, therapeutic options and prognosis. Transbronchial lung biopsies (TBLB) are often limited by small specimen size, crush artifact and other factors. Transbronchial lung cryobiopsies (TBLC) are under investigation to overcome these limitations. Methods We conducted a retrospective study of 56 patients in a single, tertiary-care academic center in order to compare the yield of both techniques when performed in the same patient. Patients underwent flexible bronchoscopy using moderate sedation with TBLB followed by TBLC in the most radiographically abnormal areas. Clinical data and post-procedural outcomes were reviewed, with a final diagnosis made utilizing a multidisciplinary approach. Results The mean age was 60 and 53.6% were male. Co-morbidities included COPD (14%) and prior malignancy (48%). The number of TBLB specimens ranged from 1–10 per patient (mean 4) and size varied from 0.1–0.8 cm. The number of TBLC specimens ranged from 1–4 per patient (mean 2) and size ranged from 0.4–2.6 cm. Both techniques provided the same diagnosis in 26 patients (46.4%). An additional 11 (19.6%) patients had a diagnosis established by adding TBLC to TBLB. Compared to TBLB, TBLC had a higher diagnostic yield in patients with hypersensitivity pneumonitis and interstitial lung disease. Only two patients required video-assisted thoracoscopic surgery (VATS) to establish a diagnosis. Complications included pneumothorax (19.6%) and massive hemoptysis (1.8%). Conclusions TBLC used with TBLB can improve the diagnostic yield of flexible bronchoscopy in patients with DPLD.

Advances in medical diagnosis reveal that coronary artery aneurysms (CAAs) may develop in several clinical scenarios and manifest variable symptoms, imaging appearances, and outcomes. Aneurysms are pathologically classified into three groups: atherosclerotic, inflammatory, and noninflammatory. The last category is associated with congenital, inherited, and connective tissue disorders. Overlap exists among the groups, because secondary atherosclerotic change may be present in an aneurysm of any cause. Atherosclerosis is the most common cause of CAAs in adults, and inflammation is considered the underlying mechanism. In children, Kawasaki disease is the most likely cause of CAAs. In both conditions, the aneurysms are usually multiple and affect more than one coronary artery. Mycotic (infectious), iatrogenic, and cocaine-induced CAAs are also well documented. Most CAAs are discovered incidentally, but potential cardiovascular complications include thrombosis, occlusion, fistula formation, rupture, myocardial infarction, and cardiac tamponade. Imaging modalities to evaluate a suspected CAA include transthoracic echocardiography, angiographic cardiac catheterization, electrocardiographically gated computed tomographic angiography, cardiac magnetic resonance (MR) imaging, and MR angiography. Management is usually individualized, and options include surveillance, anticoagulant therapy, percutaneous stent or coil placement, surgical resection, and coronary artery bypass grafting.

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