Frequency and imaging features of abdominal immune-related adverse events in metastatic lung cancer patients treated with PD-1 inhibitor

PurposeTo investigate the frequency and imaging features of radiographically evident abdominal immune-related adverse events (irAEs) in patients with metastatic non-small-cell lung cancer (NSCLC) treated with PD-1 inhibitors.MethodsThis retrospective study included 137 patients with metastatic NSCLC treated with PD-1 inhibitor nivolumab monotherapy (75 women; median age: 65years), who had a baseline CT and at least one follow-up abdomen CT during therapy. Baseline and all follow-up abdominal CTs performed for monitoring of nivolumab therapy were reviewed to identify the organ-specific abdominal irAEs including colitis/enteritis, hepatitis, biliary toxicity, pancreatitis, nephritis, sarcoid-like reaction, and pancreatic and adrenal atrophy. Their frequency and imaging features were described.ResultsEighteen (13%) patients had radiologically identified abdominal irAEs (median 2.1months after starting nivolumab; interquartile range 1.17-5.83months); 16 patients developed enteritis/colitis (12 pancolitis, two segmental colitis, one enterocolitis, one enteritis), two hepatitis, one adrenalitis. One patient with hepatitis also developed colitis/enteritis. Radiographic abdominal irAE occurred after nivolumab therapy was discontinued in six patients before any subsequent therapy was started. IrAEs prompted nivolumab interruption and treatment with steroids in four patients (three colitis/enteritis, one hepatitis). Most common CT features of colitis/enteritis included mesenteric hyperemia (n = 15), bowel wall thickening (n = 13), mucosal hyperenhancement (n = 10), and fluid-filled colon (n = 9).ConclusionAbdominal irAEs were detected on CT in 13% of NSCLC patients treated with nivolumab, and colitis, in the pancolitis form, was the most common irAE. Given the expanding role of immunotherapy, radiologists should be aware of the frequency and imaging manifestations of abdominal irAEs and the impact on patient management

Effect of transition elements on dispersoid formation and elevated-temperature mechanical properties in 6082 aluminum alloy

The effect of transition elements, specifically Mn, Cr, V, and Mo, on dispersoid formation and mechanical properties in 6082 aluminum alloy was studied. The elevated-temperature mechanical properties were evaluated based on the compressive yield strength and creep resistance. The results indicated that the addition of Mn to the 6082 alloy resulted in the formation of a large number of the thermally stable α-Al(MnFe)Si dispersoids, thereby significantly improving the elevated-temperature mechanical properties of the alloy. Subsequent additions of Cr, V, and Mo increased the amount of Mn-bearing intermetallic phases, which decreased the supersaturation levels of Mn and Si in the α-Al, and consequently decreased the volume fraction of the dispersoids. The alloys containing Cr, V, and Mo exhibited similar yield strengths at 300°C and higher yield strengths at room temperature compared to the alloy containing only Mn. The size effect of the smaller dispersoids containing Cr, V, and Mo together with the solid-solution hardening of these elements could balance out the strength decrease resulting from the decreased volume fraction of the dispersoids. The additions of Cr, V, and Mo significantly increased the creep resistance of the Mn-containing 6082 alloy. Vanadium induced the highest creep resistance followed by Cr and Mo. Solute atoms of these elements with low diffusivity in the aluminum matrix contributed significantly to increasing the creep resistance at 300°C

Genomic and pathological heterogeneity in clinically diagnosed small cell lung cancer in never/light smokers identifies therapeutically targetable alterations

Small‐cell lung cancer (SCLC) occurs infrequently in never/former light smokers. We sought to study this rare clinical subset through next‐generation sequencing (NGS) and by characterizing a representative patient‐derived model. We performed targeted NGS, as well as comprehensive pathological evaluation, in 11 never/former light smokers with clinically diagnosed SCLC. We established a patient‐derived model from one such patient (DFCI168) harboring an NRASQ61K mutation and characterized the sensitivity of this model to MEK and TORC1/2 inhibitors. Despite the clinical diagnosis of SCLC, the majority (8/11) of cases were either of nonpulmonary origin or of mixed histology and included atypical carcinoid (n = 1), mixed non‐small‐cell lung carcinoma and SCLC (n = 4), unspecified poorly differentiated carcinoma (n = 1), or small‐cell carcinoma from different origins (n = 2). RB1 and TP53 mutations were found in four and five cases, respectively. Predicted driver mutations were detected in EGFR (n = 2), NRAS (n = 1), KRAS (n = 1), BRCA1 (n = 1), and ATM (n = 1), and one case harbored a TMPRSS2‐ERG fusion. DFCI168 (NRASQ61K) exhibited marked sensitivity to MEK inhibitors in vitro and in vivo. The combination of MEK and mTORC1/2 inhibitors synergized to prevent compensatory mTOR activation, resulting in prolonged growth inhibition in this model and in three other NRAS mutant lung cancer cell lines. SCLC in never/former light smokers is rare and is potentially a distinct disease entity comprised of oncogenic driver mutation‐harboring carcinomas morphologically and/or clinically mimicking SCLC. Comprehensive pathologic review integrated with genomic profiling is critical in refining the diagnosis and in identifying potential therapeutic options