Combination of Immunotherapy and Radiotherapy-The Next Magic Step in the Management of Lung Cancer?

none4sinoneHendriks L.E.L.; Menis J.; De Ruysscher D.K.M.; Reck M.Hendriks, L. E. L.; Menis, J.; De Ruysscher, D. K. M.; Reck, M

Immunotherapy in small cell lung cancer:One step at a time: A narrative review

Chemotherapy with or without radiotherapy has been the standard of care for many years for patients with small cell lung cancer (SCLC). Despite exceptionally high responses (up to 80%) with chemotherapy, the majority of patients relapse rapidly within weeks to months after treatment completion. Therefore, new and better treatment options are necessary. Recently, synergistic activity has been reported for the addition of immune checkpoint inhibitors (ICI) to standard platinum-based chemotherapy in the therapeutic strategy of advanced SCLC. For the first time after several decades, a significant survival improvement was achieved for this population. However, the overwhelming majority of patients do not respond to ICI, or relapse rapidly. There is need for better knowledge about the biology, histopathologic features, and molecular pathways of SCLC. This can probably help to identify the optimal predictive biomarkers, which are warranted to develop an individual therapeutic strategy including the rational use of a combination of immunotherapeutic agents. Here, we provide an overview of the rationale for and clinical results of the completed and ongoing trials using different strategies of immunotherapy in SCLC. In addition, opportunities for further improvement of therapies will be discussed, including the addition of radiotherapy, co-stimulatory antibodies, and other immune modifying agents.</p

Reactions to peanut at first introduction in infancy are associated with age ≥8 months and severity of eczema

Background: Previous studies have shown the efficacy of the early introduction of peanut to prevent peanut allergy. Due to the exclusion of infants with sensitization to peanut, it remains unclear what the optimal timing of introduction is. Methods: The PeanutNL study was performed in 6 pediatric allergology centers in the Netherlands. Infants referred for the clinical early introduction of peanut to prevent peanut allergy underwent skin prick tests for peanut and an oral peanut challenge at a median age of 6 months. Results: One hundred sixty two of 707 infants (23%) who had never eaten peanut before were sensitized to peanut, of which 80 (49%) had wheals of &gt;4 mm. Sixty seven of 707 infants (9.5%) had a positive oral challenge to peanut at first introduction. Multivariate analysis revealed that age (p &lt;.001) and SCORAD eczema severity scores (p =.001) were significant risk factors. Introduction of peanut at ≥8 months in infants with moderate and severe eczema resulted in an increased risk (odds ratio 5.24 (p =.013) and 3.61 (p =.019), respectively) of having reactions to peanut as compared to introduction before 8 months. A family history of peanut allergy and previous reactions to egg were not identified as independent risk factors. Conclusion: These results suggest that peanut should be introduced before the age of 8 months to reduce the risk of reactions at first exposure in infants with moderate and severe eczema. Furthermore, since children with severe eczema have the highest risk of reactions, the clinical introduction of peanut should be considered, at the latest at the age of 7 months.</p

Effect of Systolic Blood Pressure on Left Ventricular Structure and Function A Mendelian Randomization Study

We aimed to estimate the effects of a lifelong exposure to high systolic blood pressure (SBP) on left ventricular (LV) structure and function using Mendelian randomization. A total of 5596 participants of the UK Biobank were included for whom cardiovascular magnetic resonance imaging and genetic data were available. Major exclusion criteria included nonwhite ethnicity, major cardiovascular disease, and body mass index >30 o

Agreement of 2D transthoracic echocardiography with cardiovascular magnetic resonance imaging after ST-elevation myocardial infarction

Background: This study was designed to investigate the agreement of 2D transthoracic echocardiography (2D TTE) with cardiovascular magnetic resonance imaging (CMR) in a contemporary population of ST-elevation myocardial infarction (STEMI) patients. Methods: In this subanalysis of the GIPS-III trial, a randomized controlled trial investigating the administration of metformin in STEMI patients to prevent reperfusion injury, we studied 259 patients who underwent same-day CMR and 2D TTE assessments four months after hospitalization for a first STEMI. Bland-Altman analyses were performed to assess agreement between LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV ejection fraction (LVEF), and LV mass measurements. Sensitivity and specificity of 2D TTE to detect categories of LVEF (≤35%, 35–50%, ≥50%) was determined. Linear regression of absolute differences in measurements between imaging modalities was used to investigate whether patient characteristics impact measurement bias. Results: Pairwise difference (bias) and 95% limits of agreement between CMR and 2D TTE measurements were +84 (37, 147) ml for LVEDV, +39 (6, 85) ml for LVESV, -1.1 ± 13.5% for LVEF, and -75 (-154, -14) g for LV mass. Sensitivity and specificity of 2D TTE to detect subjects with moderately depressed LVEF (35–50%) as measured by CMR were 52% and 88% respectively. We observed a significant effect of enzymatic infarct size on bias between 2D TTE and CMR in measuring LVESV and LVEF (P = 0.029, P = 0.001 respectively), of age and sex on bias between 2D TTE and CMR in measuring LV mass (P = 0.027, P < 0.001) and LVEDV (P = 0.001, P = 0.039), and of heart rate on bias between 2D TTE and CMR in LV volume measurements (P = 0.004, P = 0.016). Conclusions: Wide limits of agreement, underestimation of LV volumes and overestimation of LV mass was observed when comparing 2D TTE to CMR. Enzymatic infarct size, age, sex, and heart rate are potential sources of bias between imaging modalities

Causal Pathways from Blood Pressure to Larger Qrs Amplitudes a Mendelian Randomization Study

Abnormal QRS duration and amplitudes on the electrocardiogram are indicative of cardiac pathology and are associated with adverse outcomes. The causal nature of these associations remains uncertain and could be due to QRS abnormalities being a symptom of cardiac damage rather than a factor on the causal pathway. By performing Mendelian randomization (MR) analyses using summary statistics of genome wide association study consortia with sample sizes between 20,687 and 339,224 individuals, we aimed to determine which cardiovascular risk factors causally lead to changes in QRS duration and amplitude (Sokolow-Lyon, Cornell and 12-leadsum products). Additionally, we aimed to determine whether QRS traits have a causal relationship with mortality and longevity. We performed inverse-variance weighted MR as main analyses and MR-Egger regression and weighted median estimation as sensitivity analyses. We found evidence for a causal relationship between higher blood pressure and larger QRS amplitudes (systolic blood pressure on Cornell: 55SNPs, causal effect estimate per 1 mmHg = 9.77 millimeters.milliseconds (SE = 1.38, P = 1.20 x 10(-12)) and diastolic blood pressure on Cornell: 57SNPs, causal effect estimate per 1 mmHg = 14.89 millimeters.milliseconds (SE = 1.82, P = 3.08 x 10(-16)), but not QRS duration. Genetically predicted QRS traits were not associated with longevity, suggesting a more prominent role of acquired factors in explaining the wellknown link between QRS abnormalities and outcome