Nationwide Survival Benefit after Implementation of First-Line Immunotherapy for Patients with Advanced NSCLC—Real World Efficacy

SIMPLE SUMMARY: The expected change in overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC) after the clinical implementation of immune checkpoint inhibitor therapy (ICI) has not been substantially investigated in large real-world cohorts outside randomized controlled trials (RCTs). In this nationwide study, we compared OS before and after the implementation of ICI and found that 3-year OS tripled from 6% to 18%. Patients receiving ICI had a lower OS than demonstrated in RCTs, except for patients with performance status (PS) 0. More than a fifth of the patients progressed early within the first six ICI cycles. Adverse prognostic factors were PS ≥ 1 and metastases to the bone and liver. ABSTRACT: Background The selection of patients with non-small cell lung cancer (NSCLC) for immune checkpoint inhibitor (ICI) treatment remains challenging. This real-world study aimed to compare the overall survival (OS) before and after the implementation of ICIs, to identify OS prognostic factors, and to assess treatment data in first-line (1L) ICI-treated patients without epidermal growth factor receptor mutation or anaplastic lymphoma kinase translocation. Methods Data from the Danish NSCLC population initiated with 1L palliative antineoplastic treatment from 1 January 2013 to 1 October 2018, were extracted from the Danish Lung Cancer Registry (DLCR). Long-term survival and median OS pre- and post-approval of 1L ICI were compared. From electronic health records, additional clinical and treatment data were obtained for ICI-treated patients from 1 March 2017 to 1 October 2018. Results The OS was significantly improved in the DLCR post-approval cohort (n = 2055) compared to the pre-approval cohort (n = 1658). The 3-year OS rates were 18% (95% CI 15.6–20.0) and 6% (95% CI 5.1–7.4), respectively. On multivariable Cox regression, bone (HR = 1.63) and liver metastases (HR = 1.47), performance status (PS) 1 (HR = 1.86), and PS ≥ 2 (HR = 2.19) were significantly associated with poor OS in ICI-treated patients. Conclusion OS significantly improved in patients with advanced NSCLC after ICI implementation in Denmark. In ICI-treated patients, PS ≥ 1, and bone and liver metastases were associated with a worse prognosis

A multiple myeloma classification system that associates normal B-cell subset phenotypes with prognosis.

Despite the recent progress in treatment of multiple myeloma (MM), it is still an incurable malignant disease, and we are therefore in need of new risk stratification tools that can help us to understand the disease and optimize therapy. Here we propose a new subtyping of myeloma plasma cells (PCs) from diagnostic samples, assigned by normal B-cell subset associated gene signatures (BAGS). For this purpose, we combined fluorescence-activated cell sorting and gene expression profiles from normal bone marrow (BM) Pre-BI, Pre-BII, immature, naïve, memory, and PC subsets to generate BAGS for assignment of normal BM subtypes in diagnostic samples. The impact of the subtypes was analyzed in 8 available data sets from 1772 patients' myeloma PC samples. The resulting tumor assignments in available clinical data sets exhibited similar BAGS subtype frequencies in 4 cohorts from de novo MM patients across 1296 individual cases. The BAGS subtypes were significantly associated with progression-free and overall survival in a meta-analysis of 916 patients from 3 prospective clinical trials. The major impact was observed within the Pre-BII and memory subtypes, which had a significantly inferior prognosis compared with other subtypes. A multiple Cox proportional hazard analysis documented that BAGS subtypes added significant, independent prognostic information to the translocations and cyclin D classification. BAGS subtype analysis of patient cases identified transcriptional differences, including a number of differentially spliced genes. We identified subtype differences in myeloma at diagnosis, with prognostic impact and predictive potential, supporting an acquired B-cell trait and phenotypic plasticity as a pathogenetic hallmark of MM

SYNTHESIS AND MICROSTRUCTURE OF ZIRCONIA AEROGELS

Des gels monolithiques transparents ont été préparés dans le système Zr(OC3H7)4-CH3COOH-C3H7OH, pour des rapports molaires acide acétique/ alcoxyde compris entre 2 et 3. Des aérogels, de densité variant de 100 à 1000 kg.m-3 et de surface spécifique supérieure à 400.103 m2.kg-1, ont été obtenus par évacuation hypercritique du solvant. L'utilisation d'acide acétique permet de contrôler la réaction d'hydrolyse-condensation, l'acide modifiant le n-propoxyde à l'échelle moléculaire et produisant de l'eau par une estérification lente du propanol. La microstructure des aérogels déterminée par diffusion centrale des rayons X permet de proposer un mécanisme de croissance de type monomère-cluster, en accord avec une cinétique lente d'hydrolyse.Transparent monolithic gels were prepared in the Zr(OC3H7)4-CH3COOH-C3H7OH system for acetic acid/ alkoxide ratios ranging from 2 to 3. Aerogels, with different densities (100-1000 kg.m-3) and with surface areas higher than 400.103 m2.kg-1, were obtained by hypercritical evacuation of the solvent from these wet gels. Use of acetic acid allows the control of the hydrolysis-condensation reaction because this acid modifies the propoxide at a molecular level and produces water by a slow esterification reaction. Aerogel microstructure. as determined by small angle X-ray scattering, justifies a monomer-cluster growth mechanism which agrees with a slow hydrolysis rate

SINTERING OF MONOLITHIC CORDIERITE AEROGELS

Des aérogels de composition cordiérite ont été élaborés par séchage hypercritique de gels obtenus par hydrolyse-condensation d'une solution alcoolique d'alcoxydes de silicium, d'aluminium et de nitrate de magnésium. La structure des gels et aérogels a été comparée par diffusion centrale des rayons X. La structure des aérogels qui résulte d'un mécanisme d'agrégation de particules élémentaires denses est étudiée en fonction de la concentration initiale puis en cours de densification.Cordierite aerogels have been elaborated by hypercritical drying of gels obtained by hydrolysis-condensation of silicon and aluminium alkoxides in alcoholic solution with magnesium nitrate. The structure of gels and aerogels is compared through small angle X-ray scattering measurements. The structure of aerogels which derives from an aggregation mechanism of elementary dense particles is studied for different initial concentrations and during densification

Nationwide Survival Benefit after Implementation of First-Line Immunotherapy for Patients with Advanced NSCLC—Real World Efficacy

Background The selection of patients with non-small cell lung cancer (NSCLC) for immune checkpoint inhibitor (ICI) treatment remains challenging. This real-world study aimed to compare the overall survival (OS) before and after the implementation of ICIs, to identify OS prognostic factors, and to assess treatment data in first-line (1L) ICI-treated patients without epidermal growth factor receptor mutation or anaplastic lymphoma kinase translocation. Methods Data from the Danish NSCLC population initiated with 1L palliative antineoplastic treatment from 1 January 2013 to 1 October 2018, were extracted from the Danish Lung Cancer Registry (DLCR). Long-term survival and median OS pre- and post-approval of 1L ICI were compared. From electronic health records, additional clinical and treatment data were obtained for ICI-treated patients from 1 March 2017 to 1 October 2018. Results The OS was significantly improved in the DLCR post-approval cohort (n = 2055) compared to the pre-approval cohort (n = 1658). The 3-year OS rates were 18% (95% CI 15.6–20.0) and 6% (95% CI 5.1–7.4), respectively. On multivariable Cox regression, bone (HR = 1.63) and liver metastases (HR = 1.47), performance status (PS) 1 (HR = 1.86), and PS ≥ 2 (HR = 2.19) were significantly associated with poor OS in ICI-treated patients. Conclusion OS significantly improved in patients with advanced NSCLC after ICI implementation in Denmark. In ICI-treated patients, PS ≥ 1, and bone and liver metastases were associated with a worse prognosis