Insights into treatment-specific prognostic somatic mutations in NSCLC from the AACR NSCLC GENIE BPC cohort analysis.

BACKGROUND: Treatment of non-small lung cancer (NSCLC) has evolved in recent years, benefiting from advances in immunotherapy and targeted therapy. However, limited biomarkers exist to assist clinicians and patients in selecting the most effective, personalized treatment strategies. Targeted next-generation sequencing-based genomic profiling has become routine in cancer treatment and generated crucial clinicogenomic data over the last decade. This has made the development of mutational biomarkers for drug response possible. METHODS: To investigate the association between a patient's responses to a specific somatic mutation treatment, we analyzed the NSCLC GENIE BPC cohort, which includes 2,004 tumor samples from 1,846 patients. RESULTS: We identified somatic mutation signatures associated with response to immunotherapy and chemotherapy, including carboplatin-, cisplatin-, pemetrexed- or docetaxel-based chemotherapy. The prediction power of the chemotherapy-associated signature was significantly affected by epidermal growth factor receptor (EGFR) mutation status. Therefore, we developed an EGFR wild-type-specific mutation signature for chemotherapy selection. CONCLUSION: Our treatment-specific gene signatures will assist clinicians and patients in selecting from multiple treatment options.

Risk Factors for In-Hospital Seizures of Aneurysmal Subarachnoid Hemorrhage After Endovascular Treatment: A Real-World Study.

BACKGROUND AND PURPOSE: The occurrence of in-hospital seizures for aneurysmal subarachnoid hemorrhage (aSAH) ranges from 3.7% to 15.2%, and seizures remain an important factor affecting patient prognosis. Therefore, the timely identification of patients at a higher risk for aSAH-associated seizures after endovascular treatment is of paramount importance. This study aims to analyze the risk factors for in-hospital seizures after endovascular treatment for aSAH. METHODS: The study comprised 547 patients at 3 centers from January 2019 to September 2021. In the context of this study, 2 models were utilized: the first model involved no variable adjustment, while the second model included all potential confounders in the multivariate logistic regression analysis. Additionally, the dose-response relationship between biomarkers and seizure occurrence was assessed using restricted cubic spline. RESULTS: Among these patients, 28 (5.1%) developed seizures during hospitalization. In Model 2, the modified Fisher score (adjusted odds ratio [OR]: 3.138, 95% confidence interval [CI]: 1.226-8.036), body mass index (adjusted OR: 0.852, 95% CI: 0.749-0.970), aspect ratio (adjusted OR: 0.264, 95% CI: 0.115-0.604), and aspartate transaminase (adjusted OR: 1.017, 95% CI: 1.001-1.035) were showed as factors contributing to an increased risk of aSAH-associated seizures. CONCLUSIONS: Body mass index, aspartate transaminase, aspect ratio, modified Fisher scores, and Hunt-Hess scores were correlated with the formation of aSAH-associated seizures after endovascular treatment.

Blood inflammatory biomarkers predict in-hospital pneumonia after endovascular treatment of aneurysm in patients with aneurysmal subarachoid hemorrhage.

The systemic inflammatory response index (SIRI) is a well-known marker of systemic inflammation reflecting the body's inflammatory/immune state. The study aimed to evaluate the relationship between the SIRI on admission and aneurysmal subarachnoid hemorrhage (aSAH)-associated pneumonia and compare with other currently used bio-markers. We reviewed 562 successive patients with aneurysmal SAH who underwent endovascular treatment between January 2019 and September 2021. ASAH-associated pneumonia was diagnosed using the modified Centers for Disease Control and Prevention criteria. The SIRI on admission was calculated as monocyte count × neutrophil count / lymphocyte count. Multiple logistic regression models were used for data analysis. A total of 158 (28.11%) patients developed aSAH-associated pneumonia. Using the Multiple logistic regression analysis, a notable dose-response association was found between the elevated SIRI (fourth quartile) and aSAH-associated pneumonia (adjusted odds ratio = 6.759; 95% confidence interval [CI], 3.280-13.930; p < 0.001 [p for trend < 0.001]). The SIRI (0.701, 95% CI: 0.653-0.749) presented a higher area under the curve (AUC) than systemic immune- inflammation index (SII) (0.669, 95% CI: 0.620-0.718) (p = 0.089); neutrophil-to-lymphocyte ratio (NLR) (0.665, 95% CI: 0.616-0.714) (p = 0.035) and platelet-lymphocyte ratio (PLR) (0.587, 95% CI: 0.534-0.641) (p < 0.001). A higher SIRI on admission was associated with aSAH-associated pneumonia, which may guide further clinical trials of prophylactic antibiotic therapy.